In vitro metformin anti-neoplastic activity in epithelial ovarian cancer

Objective. Metformin, a commonly used drug in the treatment of type II diabetes, may reduce cancer risk and improve cancer prognosis. We evaluated its effect on epithelial ovarian cancer cell lines. Methods. The OVCAR-3 and OVCAR-4 cell lines were exposed to metformin with and without cisplatin. Cytotoxicity assays were performed in triplicates using the Alamar colorimetric assay. Levels of total and phosphorylated AMPK, p70S6K and S6K were evaluated by Western blotting following exposure to metformin. Results. Metformin induces dose- and time-dependent growth inhibition of OVCAR-3 and OVCAR-4 cell lines. Metformin potentiated the effect of cisplatin in vitro. Metformin growth inhibition was partly abolished by the AMPK inhibitor, compound C. Western blotting demonstrated that metformin at cytotoxic concentrations, induced AMPK phosphorylation and decreased p70S6K and S6K phosphorylation, suggesting the mechanism for its anti-proliferative action. Conclusion. Metformin significantly inhibits the growth of ovarian cancer cell lines and potentiates cisplatin. Further pre-clinical studies are being conducted to determine the applicability of metformin in the treatment of ovarian cancer. (c) 2008 Elsevier Inc. All rights reserved.