Antitumor Effect of Metformin on Ovarian Cancer Cells

Objective  To explore the antitumor effects of metformin on ovarian cancer cells in vitro, particularly on tumor cell proliferation, cell cycle, apoptosis, migration, and possible mechanism.

Methods  Ovarian cancer cell lines (A2780, CAOV3, and SKOV3) were treated with different concentrations of metformin. Their proliferation was explored using the MTT and clone formation assays, cell migration was examined using the scratch and Transwell assays, and cell cycle and apoptosis were examined using flow cytometry. In addition, metformin’s effects on the phosphorylation of AMPK and mTOR and the expression of CXCR4 and Wnt/β-catenin protein was measured by Western blot.

Results  The survival rates of ovarian cancer cells decreased significantly with increasing metformin concentration and metformin treatment time. The IC₅₀ values of metformin at 48 h for A2780, CAOV3, and SKOV3 cells were 16.36, 36.65, and 43.44 mmol/L, respectively. Compared with the control group, the clone formation ability and cell migration ability of ovarian cancer cells were significantly inhibited by metformin treatment and cell cycle arrested at the G₀/G₁ phase, and the apoptosis rate increased. As metformin concentration increased, the expression of phosphorylated AMPK protein gradually increased, and the expression levels of phosphorylated mTOR, CXCR4, Dvl3, β-catenin, cyclin D1, and CDK1 decreased.

Conclusion  Metformin exerts an antitumor effect on ovarian cancer cells, which is related to the activation of AMPK to inhibit CXCR4-mediated Wnt/β-catenin signaling pathway.