1. Department of General Dentisty, Chancheng Distric Xiangyang Hospital of Foshan, Chancheng Stomotoyical Hospital of Foshan, Foshan 528000; 2. Department of Stomatology, the Third Affiliated Hospital, Sun Yatsew University, Zhongshan 510000, Guangzhou Province, China
Objective: To investigate the inhibitory effect of metformin on human oral squamous cell carcinoma SCC-4 and CAL-27 cells. Methods: The recovery, culture and subculture of oral squamous cell carcinoma SCC-4 cell line and CAL-27 cell line were performed. The effects of metformin on the proliferation, cell activity, clone formation and growth cycle of human oral squamous cell carcinoma SCC-4 and CAL-27 cells were examined by MTT assay, flow cytometry and Western blot. Results: SCC-4 and CAL-27 were treated with metformin at 5 mmol/L for 12 h, 24 h and 48 h respectively, the proportion of cells in G0/G1 phase increased in a time-dependent manner (P<0.05), but the proportion of cells in S phase and G2/M phase decreased (P<0.05). The cell viability of SCC-4 and CAL-27 was significantly decreased and showed in a dose-dependent manner after 48 h of metformin intervention. After treated with metformin for 2 weeks, clone formation of SCC-4 and CAL-27 decreased in a dose-dependent manner (P<0.05). After SCC-4 and CAL-27 were treatedwith 5 mmol/L metformin, the level of AMPKa (Thrl72) was significantly increased. The expression of mTOR and its downstream direct acting molecules p-mTOR (Ser2448), p-S6Kl (Thr389) and p-4E-BPl (Thr37 / 46) were significantly decreased in a time-dependent manner. Conclusion: Metformin through the activating of AMPK signaling pathway to inhibits mTOR signaling pathway to suppress the cell viability, cell proliferation and clone formation of SCC-4 and CAL-27 cells.