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Drug Combination Details

General Information of the Combination (ID: C04523)
Name Resveratrol   NP Info  + Doxorubicin   Drug Info 
Structure +
Disease
Cervical cancer [ICD-11: 2C77]
Investigative [1]
Hepatocellular carcinoma [ICD-11: 2C12]
Investigative [1]
Colorectal cancer [ICD-11: 2B91]
Investigative [2]
Stomach cancer [ICD-11: 2B72]
Investigative [3]
Pancreatic cancer [ICD-11: 2C10]
Investigative [4]
Breast cancer [ICD-11: 2C60]
Investigative [5]
    Click to Show/Hide the Whole Disease Information of This Combination
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 [1]
                    Molecule(s)
                    Regulation
Down-regulation Expression ABCB1  Molecule Info 
Pathway MAP
                    In-vitro Model HeLa CVCL_0030 Endocervical adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)
Resveratrol potentiates cytotoxic properties of doxorubicin used in the study through increasing their intracellular level due to p-glycoprotein inhibition and downregulation of mdr1 gene.
                    Experiment 2 Reporting the Effect of This Combination [6]
                    Molecule(s)
                    Regulation
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BECN1  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Down-regulation Expression COX-2  Molecule Info 
Pathway MAP
Down-regulation Expression GABPA  Molecule Info 
Pathway MAP
Down-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    In-vivo Model Animals were maintained at standard condition and exponentially grown 1*106 EAC cells collected from peritoneal cavity from Ascitic mice, and were inoculated into the peritoneal cavity of fresh healthy male Swiss Albino mice.
                    Experimental
                    Result(s)
Resveratrol chemosensitizes doxorubicin in combination through inhibiting breast cancer cells proliferation and invasion, and inducing apoptosis via suppression of chronic inflammation and autophagy.
                    Experiment 3 Reporting the Effect of This Combination [4]
                    In-vitro Model PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)
The cells' viability was more affected when DOX:RES combinations containing higher contents of RES (1:2-1:5 molar ratios) were used. This can be explained by the ability of RES to reduce the P-glycoprotein (P-gp)-mediated efflux of DOX.
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Experiment 1 Reporting the Effect of This Combination [7]
                    Molecule(s)
                    Regulation
Down-regulation Expression ABCB1  Molecule Info 
Pathway MAP
Down-regulation Expression MSH3  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    In-vivo Model MCF-7/adr cells (5*105 cells in 0.1mL) suspended in serum-free medium containing 50% Matrigel were inoculated subcutaneously through 25-gauge needles into the right flank of each nude mouse.
                    Experimental
                    Result(s)
Resveratrol enhances chemosensitivity of doxorubicin in multidrug-resistant human breast cancer cells via increased cellular influx of doxorubicin.
                    Experiment 2 Reporting the Effect of This Combination [3]
                    Molecule(s)
                    Regulation
Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Up-regulation Expression CDH1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation mTOR  Molecule Info 
Pathway MAP
Up-regulation Expression PTEN  Molecule Info 
Pathway MAP
Down-regulation Expression S6K1  Molecule Info 
Pathway MAP
Up-regulation Expression TSC1  Molecule Info 
Pathway MAP
Up-regulation Expression TSC2  Molecule Info 
Pathway MAP
Down-regulation Expression VIM  Molecule Info 
Pathway MAP
                    In-vitro Model SGC-7901 CVCL_0520 Human gastric cancer Homo sapiens
MGC-803 CVCL_5334 Gastric mucinous adenocarcinoma Homo sapiens
                    In-vivo Model 1*107 SGC7901/DOX cells were injected subcutaneously into the left inguinal region of each nude mouse when the mice got five weeks old.
                    Experimental
                    Result(s)
RES serves as a novel solution to reverse the DOX-resistance of gastric cancer via preventing EMT by modulating PTEN/Akt signaling pathway.
                    Experiment 3 Reporting the Effect of This Combination [2]
                    Molecule(s)
                    Regulation
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
                    Biological
                    Regulation
Down-regulation P-gp efflux
                    In-vitro Model HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)
Resveratrol sensitize colorectal cancer cells to doxorubicin via activating apoptosis and ameliorating P-glycoprotein activity.
                    Experiment 4 Reporting the Effect of This Combination [5]
                    Molecule(s)
                    Regulation
Down-regulation Expression CDH2  Molecule Info 
Pathway MAP
Down-regulation Expression CTNNB1  Molecule Info 
Pathway MAP
Up-regulation Expression SIRT1  Molecule Info 
Pathway MAP
Down-regulation Expression VIM  Molecule Info 
Pathway MAP
                    In-vitro Model MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
MCF-10A CVCL_0598 Healthy Homo sapiens
                    Experimental
                    Result(s)
Resveratrol promotes sensitization to Doxorubicin by inhibiting epithelial-mesenchymal transition and modulating SIRT1/beta-catenin signaling pathway in breast cancer.
References
Reference 1 Resveratrol enhances the cytotoxic profile of docetaxel and doxorubicin in solid tumour cell lines in vitro. Cell Prolif. 2011 Dec;44(6):591-601.
Reference 2 Didox and resveratrol sensitize colorectal cancer cells to doxorubicin via activating apoptosis and ameliorating P-glycoprotein activity. Sci Rep. 2016 Nov 14;6:36855.
Reference 3 Resveratrol reverses Doxorubicin resistance by inhibiting epithelial-mesenchymal transition (EMT) through modulating PTEN/Akt signaling pathway in gastric cancer. J Exp Clin Cancer Res. 2017 Jan 26;36(1):19.
Reference 4 Comparative study of the therapeutic effect of Doxorubicin and Resveratrol combination on 2D and 3D (spheroids) cell culture models. Int J Pharm. 2018 Nov 15;551(1-2):76-83.
Reference 5 Resveratrol promotes sensitization to Doxorubicin by inhibiting epithelial-mesenchymal transition and modulating SIRT1/beta-catenin signaling pathway in breast cancer. Cancer Med. 2019 Mar;8(3):1246-1257.
Reference 6 Resveratrol improves the anticancer effects of doxorubicin in vitro and in vivo models: A mechanistic insight. Phytomedicine. 2016 Mar 15;23(3):233-42.
Reference 7 Resveratrol enhances chemosensitivity of doxorubicin in multidrug-resistant human breast cancer cells via increased cellular influx of doxorubicin. Biochim Biophys Acta. 2014 Jan;1840(1):615-25.
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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