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Drug Combination Details

General Information of the Combination (ID: C18543)
Name Gambogic acid   NP Info  + Cisplatin   Drug Info 
Structure +
Disease
Lung cancer [ICD-11: 2C25]
Investigative [1]
Osteosarcoma [ICD-11: 2B51]
Investigative [2]
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. Enhancing Drug Efficacy by This Combination
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Experiment 1 Reporting the Effect of This Combination [3]
                    Molecule(s)
                    Regulation
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Down-regulation Expression ERK2  Molecule Info 
Pathway MAP
Up-regulation Expression FAS  Molecule Info 
Pathway MAP
Down-regulation Expression HMOX1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation JNK1  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
Up-regulation Expression p105  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation p38 beta  Molecule Info 
Pathway MAP
Up-regulation Expression RELA  Molecule Info 
Pathway MAP
Down-regulation Expression XIAP  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
NCI-H1299 CVCL_0060 Lung large cell carcinoma Homo sapiens
                    In-vivo Model To determine the in vivo antitumour activity of GA combined with CDDP, viable A549 cells (5 * 106/100ul PBS per mouse) were subcutaneously injected into the right flank of 7- to 8-week-old male SCID mice.
                    Experimental
                    Result(s)
Gambogic acid synergistically potentiates cisplatin-induced apoptosis in non-small-cell lung cancer through suppressing NF-KappaB and MAPK/HO-1 signalling.
                    Experiment 2 Reporting the Effect of This Combination [1]
                    Molecule(s)
                    Regulation
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression LRP/LR  Molecule Info 
Pathway MAP
Down-regulation Expression SYCE1L  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)
Combination of gambogic acid with cisplatin enhances the antitumor effects on cisplatin-resistant lung cancer cells by downregulating MRP2 and LRP expression.
                    Experiment 3 Reporting the Effect of This Combination [4]
                    Molecule(s)
                    Regulation
Up-regulation Expression CASP8  Molecule Info 
Pathway MAP
Up-regulation Expression CASP9  Molecule Info 
Pathway MAP
                    In-vitro Model MG-63 CVCL_0426 Osteosarcoma Homo sapiens
HOS CVCL_0312 Osteosarcoma Homo sapiens
U2OS CVCL_0042 Osteosarcoma Homo sapiens
                    Experimental
                    Result(s)
GA could increase the chemotherapeutic effect of CDDP in human osteosarcoma treatment through inducing the cell cycle arrest and promoting cell apoptosis.
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Experiment 1 Reporting the Effect of This Combination [1]
                    Molecule(s)
                    Regulation
Down-regulation Expression ABCC1  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)
Combination of gambogic acid with cisplatin enhances the antitumor effects on cisplatin-resistant lung cancer cells by downregulating MRP2 and LRP expression.
    β. Reversing Drug Resistance by This Combination
                 Reversing Drug Resistance     Click to Show/Hide
                    Experiment 1 Reporting the Effect of This Combination [2]
                    Molecule(s)
                    Regulation
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Up-regulation Expression FAS  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation p38 beta  Molecule Info 
Pathway MAP
                    In-vitro Model MG-63 CVCL_0426 Osteosarcoma Homo sapiens
HOS CVCL_0312 Osteosarcoma Homo sapiens
                    In-vivo Model 0.2 mL of MG63 cell suspension (1.5*107 cells/ml) was subcutaneously injected into the right flank of mice.
                    Experimental
                    Result(s)
Hypoxia-induced resistance to cisplatin-mediated apoptosis in osteosarcoma cells is reversed by gambogic acid independently of HIF-1Alpha.
References
Reference 1 Combination of gambogic acid with cisplatin enhances the antitumor effects on cisplatin-resistant lung cancer cells by downregulating MRP2 and LRP expression. Onco Targets Ther. 2016 Jun 2;9:3359-68.
Reference 2 Hypoxia-induced resistance to cisplatin-mediated apoptosis in osteosarcoma cells is reversed by gambogic acid independently of HIF-1Alpha. Mol Cell Biochem. 2016 Sep;420(1-2):1-8.
Reference 3 Gambogic acid synergistically potentiates cisplatin-induced apoptosis in non-small-cell lung cancer through suppressing NF-KappaB and MAPK/HO-1 signalling. Br J Cancer. 2014 Jan 21;110(2):341-52.
Reference 4 Viability inhibition effect of gambogic acid combined with cisplatin on osteosarcoma cells via mitochondria-independent apoptotic pathway. Mol Cell Biochem. 2013 Oct;382(1-2):243-52.
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Cite NPCDR
Visitor Map
Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China