Metformin Inhibits Cisplatin-Induced Epithelial-to-Mesenchymal Transition in Chemoresistant Ovarian Cancer by Repressing Akt Signaling

Abstract

Objective: The aim of this study was to investigate the role of metformin in reversing the chemoresistance of ovarian cancer and the underlying mechanism. Material and Methods: The expression of E-cadherin、 vimentin and p-Akt in A2780 and A2780/DDP cells was determined by Western blot. The regulatory effects of metformin on proliferative and apoptosis in A2780/DDP cells were evaluated by the Cell Counting Kit 8 (CCK-8) and the Annexin V-FITC Kit. The expression of E-cadherin、vimentin and p-Akt in different groups of A2780/DDP cells was determined by Western blot. Results: The expression levels of E-cadherin were significantly lower in A2780/DDP cells than in A2780 cells (p<0.05); in contrast, the expression levels of vimentin and p-Akt were significantly higher (p<0.05). The combination of metformin and cisplatin reduced cell viability compared with cisplatin treatment only. However, the combination of cisplatin and metformin had no effect on apoptosis in A2780/DDP cells. In addition, cisplatin was shown to induce EMT in A2780/DDP cells (p<0.05), while the combination of metformin and cisplatin reversed EMT. Cisplatin was also shown to increase the expression levels of p-Akt in A2780/DDP cells (p<0.05), while the combination of metformin and cisplatin reversed the expression of p-Akt. Conclusion: Metformin can sensitize A2780/DDP cells to cisplatin by inhibiting EMT. We hypothesize that the mechanism responsible for this effect involves the inhibition of the Akt signaling pathway.