Drug Details

General Information of the Drug (ID: DR2391)
Name
Gemcitabine
Synonyms
Gemcitabine hydrochloride; DDFC; DFdC; DFdCyd; Folfugem; GEO; Gamcitabine; GemLip; Gemcel; Gemcin; Gemcitabina; Gemcitabinum; Gemtro; Gemzar; Zefei; Gemcitabine HCl; Gemcitabine stereoisomer; LY 188011; LY188011; Gemcitabina [INN-Spanish]; Gemcitabinum [INN-Latin]; Gemzar (TN); Gemzar (hydrochloride); Inno-D07001; LY-188011; Gemcitabine (USAN/INN)
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Molecular Type
Small molecule
Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z] Approved [1]
Structure
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2D MOL

3D MOL

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Formula
C9H11F2N3O4
PubChem CID
60750
Canonical SMILES
C1=CN(C(=O)N=C1N)C2C(C(C(O2)CO)O)(F)F
InChI
1S/C9H11F2N3O4/c10-9(11)6(16)4(3-15)18-7(9)14-2-1-5(12)13-8(14)17/h1-2,4,6-7,15-16H,3H2,(H2,12,13,17)/t4-,6-,7-/m1/s1
InChIKey
SDUQYLNIPVEERB-QPPQHZFASA-N
CAS Number
CAS 95058-81-4
GDSC
Gemcitabine
TTD Drug ID
D03UVS
DrugBank ID
DB00441
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          6-shogaol      Acacia confusa     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Down-regulation Expression COX-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation RELA  Molecule Info 
Pathway MAP
Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    In-vitro Model PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
BxPC-3 CVCL_0186 Pancreatic ductal adenocarcinoma Homo sapiens
                    In-vivo Model Male BALB/c immunodeficient nude mice were injected with PANC-1 cells (1*107) with matrigel (100 uL) to the right flank of each mice.
                    Experimental
                    Result(s)		 Antitumor activity of gemcitabine can be potentiated in pancreatic cancer through modulation of TLR4/NF-kappaB signaling by 6-shogaol.
          Apigenin      Psilotum nudum     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
                    In-vitro Model MIA PaCa-2 CVCL_0428 Pancreatic ductal adenocarcinoma Homo sapiens
AsPC-1 CVCL_0152 Pancreatic ductal adenocarcinoma Homo sapiens
                    In-vivo Model Male BALB/c nude mice were subcutaneously inoculated with MiaPaca-2 cells (1*106 cells/mouse) cells in 1 mL of Matrigel.
                    Experimental
                    Result(s)		 The combination of gemcitabine and apigenin enhanced anti-tumor efficacy through Akt and NF-kappa B activity suppression and apoptosis induction.
          Arsenic trioxide      Realgar and orpiment     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CORO1A  Molecule Info 
Pathway MAP
Down-regulation Expression SKP2  Molecule Info 
Pathway MAP
                    In-vitro Model PaTu 8988s CVCL_1846 Pancreatic adenocarcinoma Homo sapiens
PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Arsenic trioxide inhibits Skp2 expression to increase chemosensitivity to gemcitabine in pancreatic cancer cells.
          Brucine      Strchnos icaja     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression p105  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Brucine, either individually or in combination, but not gemcitabine, inhibited NF-kB subunit (p65) expression in MCF-7 cells.
          Bufalin      Bufo gargarizans     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression MAP3K5  Molecule Info 
Pathway MAP
                    In-vitro Model BxPC-3 CVCL_0186 Pancreatic ductal adenocarcinoma Homo sapiens
MIA PaCa-2 CVCL_0428 Pancreatic ductal adenocarcinoma Homo sapiens
PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
                    In-vivo Model To establish xenograft model, each mouse was subcutaneously injected with 6x106 Mia PaCa-2 cells in the back.
                    Experimental
                    Result(s)		 Bufalin enhances the antitumor effect of gemcitabine in pancreatic cancer.
          Cladribine      Homo sapiens     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model J45.01 CVCL_2530 T acute lymphoblastic leukemia Homo sapiens
U-937 CVCL_0007 Adult acute monocytic leukemia Homo sapiens
                    Experimental
                    Result(s)		 The Clad+Gem+Bu+SAHA combination provides synergistic cytotoxicity in lymphoma cell lines.
          Curcumin      Hellenia speciosa     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Down-regulation Expression PCNA  Molecule Info 
Pathway MAP
                    In-vitro Model BxPC-3 CVCL_0186 Pancreatic ductal adenocarcinoma Homo sapiens
MIA PaCa-2 CVCL_0428 Pancreatic ductal adenocarcinoma Homo sapiens
PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
                    In-vivo Model Xenograft tumors were generated by subcutaneous injection of 1*106 BxPC3-GEMR cells in male athymic nude mice.
                    Experimental
                    Result(s)		 Curcumin sensitizes pancreatic cancer cells to gemcitabine by attenuating PRC2 subunit EZH2, and the lncRNA PVT1 expression.
          Dicoumarol      Vanilla fragrans     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression NQO1  Molecule Info 
Pathway MAP
                    In-vitro Model KKU-100 CVCL_3996 Hilar cholangiocarcinoma Homo sapiens
KKU-OCA17 CVCL_M265 Intrahepatic cholangiocarcinoma Homo sapiens
KKU-213B CVCL_M264 Cholangiocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 NQO1 may be important in sensitizing cells to anticancer drugs and inhibition of NQO1 may be a strategy for the treatment of CCA.
          Emodin      Oplopanax elatus     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression p105  Molecule Info 
Pathway MAP
Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    In-vitro Model SW1990 CVCL_1723 Pancreatic adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Emodin enhances the antitumor effect of gemcitabine in SW1990 pancreatic cancer in vitro and in vivo, which may be via the downregulation of NF-kappaB expression, thus inhibiting the expression of XIAP.
          Epigallocatechin gallate      Hamamelis virginiana     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression CDH2  Molecule Info 
Pathway MAP
Down-regulation Expression VIM  Molecule Info 
Pathway MAP
                    In-vitro Model PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
MIA PaCa-2 CVCL_0428 Pancreatic ductal adenocarcinoma Homo sapiens
BxPC-3 CVCL_0186 Pancreatic ductal adenocarcinoma Homo sapiens
HPAF-II CVCL_0313 Pancreatic ductal adenocarcinoma Homo sapiens
CFPAC-1 CVCL_1119 Cystic fibrosis Homo sapiens
SU.86.86 CVCL_3881 Pancreatic adenocarcinoma Homo sapiens
KPC3 CVCL_A9ZK Mouse pancreatic neoplasm Mus musculus
                    In-vivo Model C57BL/6J mice (4-6 weeks) were injected subcutaneously with 0.3*106 KPC cells per tumor suspended in 100L of sterile PBS.
                    Experimental
                    Result(s)		 EGCG synergized with gemcitabine to suppress pancreatic cancer cell growth, migration, and invasion, through modulating epithelial-mesenchymal transition markers and inhibiting Akt pathway.
          Eugenol      Coreopsis tinctoria     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [12]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression COX-2  Molecule Info 
Pathway MAP
Down-regulation Expression IL1B  Molecule Info 
Pathway MAP
                    In-vitro Model HeLa CVCL_0030 Endocervical adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Eugenol enhances the chemotherapeutic potential of gemcitabine and induces anticarcinogenic and anti-inflammatory activity in human cervical cancer cells.
          Fisetin      Toxicodendron succedaneum     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [13]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CASP7  Molecule Info 
Pathway MAP
Down-regulation Expression ERK1  Molecule Info 
Pathway MAP
Down-regulation Expression ERK2  Molecule Info 
Pathway MAP
Down-regulation Expression MYC  Molecule Info 
Pathway MAP
                    In-vitro Model MIA PaCa-2 CVCL_0428 Pancreatic ductal adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Fisetin sensitized human pancreatic cancer cells to gemcitabine-induced cytotoxicity through inhibition of ERK-MYC signaling.
          Flavopiridol      Dysoxylum binectariferum     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [14]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression E2F1  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression RRM2  Molecule Info 
Pathway MAP
                    In-vitro Model MKN74 CVCL_2791 Gastric tubular adenocarcinoma Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
Capan-2 CVCL_0026 Pancreatic ductal adenocarcinoma Homo sapiens
SK-GT-5 CVCL_8114 Gastric adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Flavopiridol increases sensitization to gemcitabine in human gastrointestinal cancer cell lines and correlates with down-regulation of ribonucleotide reductase M2 subunit (RR-M2).
          Fucoidan      Undaria pinnatifida     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [15]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model SK-UT-1 CVCL_0533 Uterine corpus leiomyosarcoma Homo sapiens
MES-SA CVCL_1404 Uterine corpus sarcoma Homo sapiens
                    Experimental
                    Result(s)		 Isobolographic analysis demonstrates the additive and synergistic effects of gemcitabine combined with fucoidan in uterine sarcomas and carcinosarcoma cells.
          Gambogic acid      Garcinia morella     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [16]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAK  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression RRM2  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
NCI-H1299 CVCL_0060 Lung large cell carcinoma Homo sapiens
                    In-vivo Model The tumor xenografts were established by injecting 2 * 107 A549 cells per mouse in 100 ul DMEM medium and Matrigel (Corning Inc., Corning, NY) in 1:1 ratio on the dorsal flank of athymic male nude mice (6-8-week-old).
                    Experimental
                    Result(s)		 Gambogic acid potentiates gemcitabine induced anticancer activity in non-small cell lung cancer.
          Genistein      Glycine max     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [17]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
                    In-vitro Model MNNG/HOS Cl #5 CVCL_0439 Osteosarcoma Homo sapiens
                    Experimental
                    Result(s)		 Genistein potentiates the anti-cancer effects of gemcitabine in human osteosarcoma via the downregulation of Akt and nuclear factor-KappaB pathway.
          Geraniol      Rosa rugosa     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [18]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model BxPC-3 CVCL_0186 Pancreatic ductal adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Geraniol significantly increased the antiproliferative and apoptosis-inducing effects of gemcitabine on BXPC-3 cells.
          Ginsenoside Rg3      Panax ginseng     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [19]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression PECAM1  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vivo Model 0.2 mL Lewis lung carcinoma cell suspensions (1*107/mL) were injected subcutaneously into the armpit of right anterior superior limbs of female C57BL/6 mice.
                    Experimental
                    Result(s)		 Ginsenoside Rg3 combined with gemcitabine may significantly inhibit angiogenesis and growth of lung cancer and improve survival and quality of life of tumor-bearing mice.
          Guggulsterone      Commiphora mukul     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [20]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
                    In-vitro Model MIA PaCa-2 CVCL_0428 Pancreatic ductal adenocarcinoma Homo sapiens
PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
                    In-vivo Model To ceate the subcutaneous xenograft model, mice were subcutaneously inoculated with MiaPaCa-2 cells (1*106cells/mouse) in 1 mL of Matrigel.
                    Experimental
                    Result(s)		 The combination of guggulsterone to gemcitabine enhanced antitumor efficacy through apoptosis induction by suppressing Akt and nuclear factor KappaB activity and by modulating apoptosis-related protein expression in pancreatic cancer.
          Honokiol      Magnolia officinalis     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [21]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation NFKBIA  Molecule Info 
Pathway MAP
                    Experimental
                    Result(s)		 Honokiol arrests cell cycle, induces apoptosis, and potentiates the cytotoxic effect of gemcitabine in human pancreatic cancer cells.
          Luteolin      Abrus precatorius     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [22]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression GSK-3B  Molecule Info 
Pathway MAP
Down-regulation Expression KRAS  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation Cytochrome c release
                    In-vitro Model BxPC-3 CVCL_0186 Pancreatic ductal adenocarcinoma Homo sapiens
                    In-vivo Model Male athymic nude mice were inoculated with BxPC-3 cells (1*106 cells/mouse) cells.
                    Experimental
                    Result(s)		 Combination of luteolin and gemcitabine promoted apoptotic cell death in pancreatic tumor cells in vivo through inhibition of the K-ras/GSK-3beta/NF-kappaB signaling pathway, leading to a reduction in the Bcl-2/Bax ratio, release of cytochrome c, and activation of caspase 3.
          Noscapine      Papaver somniferum     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [23]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression BID  Molecule Info 
Pathway MAP
Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CASP8  Molecule Info 
Pathway MAP
Up-regulation Expression CASP9  Molecule Info 
Pathway MAP
Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression PARP1  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
NCI-H460 CVCL_0459 Lung large cell carcinoma Homo sapiens
                    In-vivo Model For a xenograft model, 3*106 human H460 cells were injected subcutaneously into the right flanks of the mice.
                    Experimental
                    Result(s)		 Nos potentiated the anticancer activity of Gem in an additive to synergistic manner against lung cancer via antiangiogenic and apoptotic pathways.
          Paclitaxel      Taxus brevifolia     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [24]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Clinical trial review
                    Experimental
                    Result(s)		 The combination was very well tolerated and was not associated with any adverse impact in quality of life compared with paclitaxel alone.
          Piceatannol      Rhodomyrtus tomentosa     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [25]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAK  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Piceatannol can enhance the cytotoxic effects of gemcitabine by enhancing expression of the proapoptotic protein Bak.
          Pristimerin      Pristimera indica     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [26]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation CHK1  Molecule Info 
Pathway MAP
Down-regulation Expression TP53BP1  Molecule Info 
Pathway MAP
                    In-vitro Model AsPC-1 CVCL_0152 Pancreatic ductal adenocarcinoma Homo sapiens
BxPC-3 CVCL_0186 Pancreatic ductal adenocarcinoma Homo sapiens
PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Pristimerin synergizes with gemcitabine through abrogating Chk1/53BP1-mediated DNA repair in pancreatic cancer cells.
          Resveratrol      Gnetum parvifolium     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [27]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Down-regulation Expression COX-2  Molecule Info 
Pathway MAP
Down-regulation Expression MMP-9  Molecule Info 
Pathway MAP
Down-regulation Expression MYC  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vitro Model AsPC-1 CVCL_0152 Pancreatic ductal adenocarcinoma Homo sapiens
MIA PaCa-2 CVCL_0428 Pancreatic ductal adenocarcinoma Homo sapiens
PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
MDA-Panc-28 CVCL_3917 Pancreatic adenocarcinoma Homo sapiens
                    In-vivo Model A small left abdominal flank incision was made in male athymic nu/nu mice, and MIA PaCa-2 cells (2*106) in 50 uL PBS were injected into the subcapsular region of the pancreas.
                    Experimental
                    Result(s)		 Resveratrol can potentiate the effects of gemcitabine through suppression of markers of proliferation, invasion, angiogenesis and metastasis.
          Salinomycin      Streptomyces albus     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [28]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model SW1990 CVCL_1723 Pancreatic adenocarcinoma Homo sapiens
AsPC-1 CVCL_0152 Pancreatic ductal adenocarcinoma Homo sapiens
                    In-vivo Model SW1990 cells were injected subcutaneously into the right flank of nude mice using a 23-gauge needle at a 2*106 cells per mouse.
                    Experimental
                    Result(s)		 Salinomycin combined with gemcitabine could eliminate the engraftment of human pancreatic cancer more effectively than the individual agents.
          Shikonin      Lithospermum erythrorhizon     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [29]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Up-regulation Activity CASP3  Molecule Info 
Pathway MAP
Up-regulation Activity CASP9  Molecule Info 
Pathway MAP
Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Down-regulation Expression COX-2  Molecule Info 
Pathway MAP
Down-regulation Expression MMP-9  Molecule Info 
Pathway MAP
Down-regulation Expression MYC  Molecule Info 
Pathway MAP
Down-regulation Activity p105  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    In-vitro Model PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
BxPC-3 CVCL_0186 Pancreatic ductal adenocarcinoma Homo sapiens
AsPC-1 CVCL_0152 Pancreatic ductal adenocarcinoma Homo sapiens
                    In-vivo Model Tumors were established by subcutaneous injection of 5*106 BxPC-3 cells into the flanks of male nude BALB/c mice.
                    Experimental
                    Result(s)		 Shikonin can suppress the growth of human pancreatic tumors and potentiate the antitumor effects of gemcitabine through the suppression of NF-kappaB and NF-kappaB-regulated gene products.
          Thymoquinone      Nigella sativa     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [30]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CASP9  Molecule Info 
Pathway MAP
Down-regulation Expression mTOR  Molecule Info 
Pathway MAP
Down-regulation Expression NOTCH1  Molecule Info 
Pathway MAP
Down-regulation Expression PSMC4  Molecule Info 
Pathway MAP
Up-regulation Expression PTEN  Molecule Info 
Pathway MAP
Down-regulation Expression RELA  Molecule Info 
Pathway MAP
Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation Cytochrome c release
                    In-vitro Model PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
AsPC-1 CVCL_0152 Pancreatic ductal adenocarcinoma Homo sapiens
BxPC-3 CVCL_0186 Pancreatic ductal adenocarcinoma Homo sapiens
                    In-vivo Model PANC-1 cells (1*106 cells/50 ll) were injected into the pancreatic parenchyma of female BALB/c nude mice.
                    Experimental
                    Result(s)		 Thymoquinone pretreatment overcomes the insensitivity and potentiates the antitumor effect of gemcitabine through abrogation of Notch1, PI3K/Akt/mTOR regulated signaling pathways in pancreatic cancer.
          Triptolide      Tripterygium hypoglaucum     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [31]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression CHK1  Molecule Info 
Pathway MAP
Up-regulation Expression H2AFX  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
                    In-vitro Model BxPC-3 CVCL_0186 Pancreatic ductal adenocarcinoma Homo sapiens
PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Triptolide synergistically increased gemcitabine-induced cell growth inhibition and apoptosis, in addition to the cooperative regulation of B-cell lymphoma 2 family proteins and loss of mitochondrial membrane potential.
          Ursolic acid      Potentilla indica     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [32]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Down-regulation Expression CFLAR  Molecule Info 
Pathway MAP
Down-regulation Expression COX-2  Molecule Info 
Pathway MAP
Down-regulation Expression ICAM1  Molecule Info 
Pathway MAP
Down-regulation Expression MMP-9  Molecule Info 
Pathway MAP
Down-regulation Expression MYC  Molecule Info 
Pathway MAP
Down-regulation Activity p105  Molecule Info 
Pathway MAP
Down-regulation Expression STAT3  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    In-vitro Model AsPC-1 CVCL_0152 Pancreatic ductal adenocarcinoma Homo sapiens
MIA PaCa-2 CVCL_0428 Pancreatic ductal adenocarcinoma Homo sapiens
MDA-Panc-28 CVCL_3917 Pancreatic adenocarcinoma Homo sapiens
                    In-vivo Model A small incision was made in the left abdominal flank of male athymic nu/nu mice, and luciferase transfected Panc-28 cells (1*106) in 50L PBS were injected into the subcapsular region of the pancreas with a 27-gauge needle.
                    Experimental
                    Result(s)		 Ursolic acid inhibits the growth of human pancreatic cancer and enhances the antitumor potential of gemcitabine in an orthotopic mouse model through suppression of the inflammatory microenvironment.
    β. A List of Natural Product(s) Able to Reverse the Resistance of This Drug
          Apicidin      Fusarium sp.     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [33]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model Capan-1 CVCL_0237 Pancreatic ductal adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Apicidin sensitizes pancreatic cancer cells to gemcitabine by epigenetically regulating MUC4 expression.
          Cyclopamine      Veratrum californicum     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [34]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression Gli1  Molecule Info 
Pathway MAP
                    In-vitro Model SW1990 CVCL_1723 Pancreatic adenocarcinoma Homo sapiens
CFPAC-1 CVCL_1119 Cystic fibrosis Homo sapiens
                    Experimental
                    Result(s)		 Gemcitabine-resistant pancreatic cancer cells highly express CSCs markers and some of the HH members, and inhibition of HH by cyclopamine is an effective method of reversing gemcitabine resistance in pancreatic cancer.
          Gossypol      Gossypium herbaceum     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [35]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Up-regulation Expression PMAIP1  Molecule Info 
Pathway MAP
                    In-vitro Model CNE-1 CVCL_6888 Human nasopharyngeal carcinoma Homo sapiens
CNE-2 CVCL_6889 Human nasopharyngeal carcinoma Homo sapiens
HK-1 CVCL_7047 Lung large cell carcinoma Homo sapiens
AGS CVCL_0139 Gastric adenocarcinoma Homo sapiens
SNU-1 CVCL_0099 Gastric adenocarcinoma Homo sapiens
YCC-16 CVCL_9649 Gastric adenocarcinoma Homo sapiens
SK-BR-3 CVCL_0033 Breast adenocarcinoma Homo sapiens
T-47D CVCL_0553 Invasive breast carcinoma Homo sapiens
MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
HONE Nasopharyngeal carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combination therapy with gossypol reveals synergism against gemcitabine resistance in cancer cells with high BCL-2 expression.
Target and Pathway
Target(s) Ribonucleoside-diphosphate reductase M2 (RRM2)  Molecule Info  [36]
BioCyc Pyrimidine deoxyribonucleotides biosynthesis from CTP Click to Show/Hide
2 Pyrimidine deoxyribonucleotides de novo biosynthesis
3 Guanosine nucleotides de novo biosynthesis
4 Superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis
5 Superpathway of purine nucleotide salvage
6 Purine nucleotides de novo biosynthesis
7 Adenosine deoxyribonucleotides de novo biosynthesis
8 Guanosine deoxyribonucleotides de novo biosynthesis
KEGG Pathway Purine metabolism Click to Show/Hide
2 Pyrimidine metabolism
3 Glutathione metabolism
4 Metabolic pathways
5 p53 signaling pathway
NetPath Pathway EGFR1 Signaling Pathway Click to Show/Hide
Panther Pathway p53 pathway Click to Show/Hide
2 De novo purine biosynthesis
3 De novo pyrimidine deoxyribonucleotide biosynthesis
Pathwhiz Pathway Purine Metabolism Click to Show/Hide
2 Pyrimidine Metabolism
Pathway Interaction Database E2F transcription factor network Click to Show/Hide
Reactome E2F mediated regulation of DNA replication Click to Show/Hide
2 G1/S-Specific Transcription
WikiPathways Nucleotide Metabolism Click to Show/Hide
2 Retinoblastoma (RB) in Cancer
3 Metabolism of nucleotides
4 Fluoropyrimidine Activity
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4793).
Reference 2 Antitumor activity of gemcitabine can be potentiated in pancreatic cancer through modulation of TLR4/NF-kappaB signaling by 6-shogaol. AAPS J. 2014 Mar;16(2):246-57.
Reference 3 Enhanced anti-tumor effect of combination therapy with gemcitabine and apigenin in pancreatic cancer. Cancer Lett. 2008 Jan 18;259(1):39-49.
Reference 4 Arsenic trioxide inhibits Skp2 expression to increase chemosensitivity to gemcitabine in pancreatic cancer cells. Am J Transl Res. 2019 Feb 15;11(2):991-997.
Reference 5 Anticancer effects of brucine and gemcitabine combination in MCF-7 human breast cancer cells. Nat Prod Res. 2015;29(5):484-90.
Reference 6 Bufalin enhances the antitumor effect of gemcitabine in pancreatic cancer. Oncol Lett. 2012 Oct;4(4):792-798.
Reference 7 Cladribine, gemcitabine, busulfan, and SAHA combination as a potential pretransplant conditioning regimen for lymphomas: A preclinical study. Exp Hematol. 2016 Jun;44(6):458-65.
Reference 8 Curcumin sensitizes pancreatic cancer cells to gemcitabine by attenuating PRC2 subunit EZH2, and the lncRNA PVT1 expression. Carcinogenesis. 2017 Oct 1;38(10):1036-1046.
Reference 9 Dicoumarol enhances gemcitabine-induced cytotoxicity in high NQO1-expressing cholangiocarcinoma cells. World J Gastroenterol. 2010 May 21;16(19):2362-70.
Reference 10 Enhanced antitumor efficacy by the combination of emodin and gemcitabine against human pancreatic cancer cells via downregulation of the expression of XIAP in vitro and in vivo. Int J Oncol. 2011 Nov;39(5):1123-31.
Reference 11 Epigallocatechin-3-Gallate (EGCG) Suppresses Pancreatic Cancer Cell Growth, Invasion, and Migration partly through the Inhibition of Akt Pathway and Epithelial-Mesenchymal Transition: Enhanced Efficacy when Combined with Gemcitabine. Nutrients. 2019 Aug 9;11(8):1856.
Reference 12 Eugenol enhances the chemotherapeutic potential of gemcitabine and induces anticarcinogenic and anti-inflammatory activity in human cervical cancer cells. Cancer Biother Radiopharm. 2011 Oct;26(5):519-27.
Reference 13 Fisetin Enhances the Cytotoxicity of Gemcitabine by Down-regulating ERK-MYC in MiaPaca-2 Human Pancreatic Cancer Cells. Anticancer Res. 2018 Jun;38(6):3527-3533.
Reference 14 Flavopiridol increases sensitization to gemcitabine in human gastrointestinal cancer cell lines and correlates with down-regulation of ribonucleotide reductase M2 subunit. Clin Cancer Res. 2001 Aug;7(8):2527-36.
Reference 15 Isobolographic Analysis Demonstrates the Additive and Synergistic Effects of Gemcitabine Combined with Fucoidan in Uterine Sarcomas and Carcinosarcoma Cells. Cancers (Basel). 2019 Dec 31;12(1):107.
Reference 16 Gambogic acid potentiates gemcitabine induced anticancer activity in non-small cell lung cancer. Eur J Pharmacol. 2020 Dec 5;888:173486.
Reference 17 Genistein potentiates the anti-cancer effects of gemcitabine in human osteosarcoma via the downregulation of Akt and nuclear factor-KappaB pathway. Anticancer Agents Med Chem. 2012 Jun;12(5):554-63.
Reference 18 Inhibitory effect of geraniol in combination with gemcitabine on proliferation of BXPC-3 human pancreatic cancer cells. J Int Med Res. 2013 Aug;41(4):993-1001.
Reference 19 Inhibitory effect of ginsenoside Rg3 combined with gemcitabine on angiogenesis and growth of lung cancer in mice. BMC Cancer. 2009 Jul 23;9:250.
Reference 20 Enhanced antitumor effect of combination therapy with gemcitabine and guggulsterone in pancreatic cancer. Pancreas. 2012 Oct;41(7):1048-57.
Reference 21 Honokiol arrests cell cycle, induces apoptosis, and potentiates the cytotoxic effect of gemcitabine in human pancreatic cancer cells. PLoS One. 2011;6(6):e21573.
Reference 22 Luteolin and Gemcitabine Protect Against Pancreatic Cancer in an Orthotopic Mouse Model. Pancreas. 2015 Jan;44(1):144-51.
Reference 23 Enhanced anticancer activity of gemcitabine in combination with noscapine via antiangiogenic and apoptotic pathway against non-small cell lung cancer. PLoS One. 2011;6(11):e27394.
Reference 24 Gemcitabine plus paclitaxel in breast cancer. Semin Oncol. 2005 Aug;32(4 Suppl 6):S14-21.
Reference 25 Piceatannol Enhances the Antitumor Efficacy of Gemcitabine in Human A549 Non-Small Cell Lung Cancer Cells. Oncol Res. 2014;22(4):213-217.
Reference 26 Pristimerin synergizes with gemcitabine through abrogating Chk1/53BP1-mediated DNA repair in pancreatic cancer cells. Food Chem Toxicol. 2021 Jan;147:111919.
Reference 27 Resveratrol, a multitargeted agent, can enhance antitumor activity of gemcitabine in vitro and in orthotopic mouse model of human pancreatic cancer. Int J Cancer. 2010 Jul 15;127(2):257-68.
Reference 28 Combination of salinomycin and gemcitabine eliminates pancreatic cancer cells. Cancer Lett. 2011 Dec 27;313(2):137-44.
Reference 29 Shikonin suppresses tumor growth and synergizes with gemcitabine in a pancreatic cancer xenograft model: Involvement of NF-kappaB signaling pathway. Biochem Pharmacol. 2014 Apr 1;88(3):322-33.
Reference 30 Thymoquinone Pretreatment Overcomes the Insensitivity and Potentiates the Antitumor Effect of Gemcitabine Through Abrogation of Notch1, PI3K/Akt/mTOR Regulated Signaling Pathways in Pancreatic Cancer. Dig Dis Sci. 2015 Apr;60(4):1067-80.
Reference 31 Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells. Oncol Lett. 2016 May;11(5):3527-3533.
Reference 32 Ursolic acid inhibits the growth of human pancreatic cancer and enhances the antitumor potential of gemcitabine in an orthotopic mouse model through suppression of the inflammatory microenvironment. Oncotarget. 2016 Mar 15;7(11):13182-96.
Reference 33 Apicidin sensitizes pancreatic cancer cells to gemcitabine by epigenetically regulating MUC4 expression. Anticancer Res. 2014 Oct;34(10):5269-76.
Reference 34 Cyclopamine reverts acquired chemoresistance and down-regulates cancer stem cell markers in pancreatic cancer cell lines. Swiss Med Wkly. 2011 May 31;141:w13208.
Reference 35 Combination therapy with gossypol reveals synergism against gemcitabine resistance in cancer cells with high BCL-2 expression. PLoS One. 2012;7(12):e50786.
Reference 36 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
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