Metformin inhibits proliferation and migration of endometrial cancer cells through regulating PI3K/AKT/MDM2 pathway.

Abstract

To investigate the influences of metformin on the proliferation and migration of endometrial cancer (EC) Ishikawa cells and its mechanism. After the EC Ishikawa cells were treated with metformin at a concentration of 10 mM for 24 h, the proliferation of cancer cells was detected via XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-car-boxanilide] assay and colony formation assay, and the migration and invasion of cancer cells were detected via wound healing assay and transwell assay. In addition, the expressions of epithelial-mesenchymal transition (EMT)-related proteins, E-cadherin and Vimentin, were detected via Western blotting, and immunofluorescence staining was performed for E-cadherin in cancer cells. Finally, the protein expression level of phosphatidylinositol 3-hydroxy kinase/protein kinase B/murine double minute 2 (PI3K/AKT/MDM2) signaling pathway in cancer cells was detected via Western blotting. Metformin inhibited the proliferation of Ishikawa cells in a concentration-dependent manner (0-10 mM) (p<0.05). Moreover, metformin (10 mM) also inhibited the proliferation of Ishikawa cells in a time-dependent manner (0-72 h) (p<0.05). The results of colony formation assay revealed that metformin (10 mM) could significantly inhibit the colony formation of Ishikawa cells (p<0.05). The results of wound healing assay and transwell assay showed that metformin (10 mM) significantly inhibited the migration and invasion of Ishikawa cells (p<0.05). According to further studies, metformin (10 mM) inhibited the EMT process in Ishikawa cells. Western blotting results manifested that the activation of PI3K/AKT/MDM2 signaling pathway was inhibited by metformin (p<0.05). Metformin can inhibit the proliferation and migration of EC cells by inhibiting the activation of PI3K/AKT/MDM2 signaling pathway. Therefore, metformin is expected to be a new drug for the clinical treatment of EC.