Metformin And Rosiglitazone Sensitize The Anti-tumour Effect Of Doxorubicin On MCF-7 Breast Cancer Cells

Background and purpose:Previous studies have demonstrated that anti-diabetic drugs,metformin and rosiglitazone,which known as insulin-sensitizing agents,have the anticancer effect and chemosensitization effect in breast cancer via several different mechanisms,meanwhile insulin may induce proliferation of breast cancer cells.We hypothesized that metformin and rosiglitazone might have a chemosensitization role in MCF-7 breast cancer cells by insulin-sensitizing.Therefore,there is another possible anticancer mechanism that metformin and rosiglitazone may exert chemosensitization effect by insulin-sensitizing effect.In this study,we investigated the anticancer effect of metformin and rosiglitazone cooperated with doxorubicin on MCF-7 breast cancer cells by insulin-sensitizing.Methods:MCF-7 breast cancer cells were treated with different concentration of metformin(0,5,10,20,30 and 40 mM),rosiglitazone(0,5,10,30,50 and100 μM)and doxorubicin(0,0.1,1,5,10 and 20 μM)to select anappropriate experimental concentration.After MCF-7 cells were treated with the optimum experimental concentration,CCK-8 assay was used to analyze the cell proliferative activity,flow cytometry assay was used to analyze cell cycle,Hoechst 33258 staining and flow cytometry assay were used to analyze the apoptosis.Results:We found that metformin,rosiglitazone and doxorubicin individually inhibited MCF-7 breast cancer cells proliferation and induce apoptosis by time-and dose-dependent manners(p<0.05).Meanwhile,we observed chemosensitive effect when metformin and rosiglitazone respectively cooperated with doxorubicin(p<0.05).Furthermore,after being treated together with insulin,metformin and rosiglitazone also exert significant anticancer effect of doxorubicin(p<0.05).Conclusion:In conclusion,these results demonstrated that metformin and rosiglitazone inhibit proliferative activity and induce apoptosis of MCF-7breast cancer cells.Metformin and rosiglitazone enhance the chemotherapeutic effect,which could be attributed to insulin-sensitizing effect.Our study suggests a possible new approach of adjuvant treatment for breast cancer patients.