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

P. Qiang, Y. Shao, Y.-P. Sun, J. Zhang, L.-J. Chen

Department of Gynecology, The First People’s Hospital of Zhangjiagang, Zhangjiagang Affiliated Hospital of Soochow University, Zhangjiagang, China. 30505543@qq.com

---

• Pharmacology

OBJECTIVE: To investigate the influences of metformin on the proliferation and migration of endometrial cancer (EC) Ishikawa cells and its mechanism.

MATERIALS AND METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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.

Free PDF Download