Effect of metformin combined with paclitaxel on apoptosis and AMPK signaling in human breast cancer cells

AIM:To investigate the effect of metformin combined with paclitaxel on the viability and apoptosis of breast cancer cell line MCF-7 and its possible mechanism. METHODS:MCF-7 cells were treated with metformin at different concentrations (2, 5, 10, 20, 40 and 80 mmol/L) and in vitro cultured. The viability of MCF-7 cells was measured by MTT assay. Metformin at 2 mmol/L or paclitaxel at 2.4 mg/L alone or in combination was used to treat the cells, and compound C, an inhibitor of adenosine monophosphate-activated protein kinase (AMPK) signaling transduction pathway, was also used. The cells were divided into control group, metformin group, paclitaxel group, combination group, and combination +compound C group. The apoptosis of the cells was analyzed by flow cytometry. The expression of Bax, Bcl-2 and caspase-3 at mRNA and protein levels was determined by RT-qPCR and Western blot. The protein levels of AMPK and P21 were examined by Western blot. RESULTS:Metformin at different concentrations (2, 5, 10, 20, 40 and 80 mmol/L) significantly inhibited the cell viability in a concentration-dependent manner (P<0.05). Compared with control group, treatment with metformin at 2 mmol/L or paclitaxel at 2.4 mg/L alone or in combination significantly inhibited the cell viability, induced apoptosis (P<0.05), decreased the level of Bcl-2 (P<0.05), increased the levels of Bax and caspase-3 (P<0.05), and promoted the protein expression of AMPK and P21 (P<0.05). The effects of metformin and paclitaxel in combination were better than those of single drug treatment, while AMPK inhibitor weaken these effects. CONCLUSION:Metformin combined with paclitaxel inhibits the viability and induces the apoptosis of breast cancer MCF-7 cells by activating AMPK signaling pathway and regulating apoptosis signaling pathway.