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Metformin Sensitizes Ovarian Cancer Cells to Chemotherapy By Inhibiting ERCC1 Expression

Cuili Zhang, Xiaofeng Li, Haonan Li, Yongqi Liang, Jing Zhang, Likun Liu and Weiling Li

Metformin is an oral anti-hyperglycemic agent of the biguanide family, which is used first-line for type II diabetes with few side-effects. Clinical studies demonstrated that diabetics taking metformin significantly decreased incidence of cancer, which has opened the prologue of metformin in cancer research. Since recent studies have revealed the inhibition of cancer cells’ growth and remission time prolonged effect of the anti-diabetic reagent metformin but the underlying mechanisms of ovarian cancer remain unclear, we investigated the potential effects and possible molecular mechanisms of metformin on chemosensitivity of ovarian cancer cells. Cell proliferation were determined with combination of cisplatin and metformin by MTT and ERCC1 expression level were analyzed by Western blotting assay. In addition, ERCC1 plasmid transfection was used to explore ERCC1 roles in the synergistic effect of cisplatin and metformin on ovarian cancer cells. The results indicated that treatment with metformin enhanced the sensitivity of ovarian cells to cisplatin and cisplatin induced ERCC1 expression could be suppressed by metformin. Furthermore, over-expression of ERCC1 in ovarian cancer cells could abrogate the synergistic effect of cisplatin and metformin. In conclusion, metformin enhanced the sensitivity of ovarian cancer cells to cisplatin by down-regulation the expression of ERCC1 and may be a prospective chemotherapeutic agent or a chemosensitizer in future ovarian cancer treatment.