Abstract: Objective To investigate the effects and mechanism of metformin(Met) on the proliferation of cervical squamous cell carcinoma. Methods CCK-8 method was used to check the proliferation of cells lines SiHa and CaSKi, the semi inhibitory concentration of metformin (IC₅₀) was calculated as well.The cell cycle and apoptosis were examined by flow cytometry, and the expression of AMPK-mTOR signal pathway related proteins was detected by Western blot. Results With the increase of drug concentration and time, the cell proliferation rate decreased(P＜0.05).The IC₅₀ concentrations of SiHa cells at 48 and 72 h were (50.95±2.63) and (21.39±5.23) mmol/L respectively, and those of CaSki cells were (9.98±1.63) and (7.47±2.09)mmol/L, resepectively. The content of G₂/M phase cells decreased and S phase cells increased in Met group (P＜ 0.05). The apoptosis rate of Met group was higher than that of control group (P＜ 0.05). The expression of p-AMPK in the Met group was higher than that in the control group, while p-S6K and p-4E-BP1 were lower(P＜ 0.05). Conclusions The inhibitory effect of metformin on the proliferation of cervical squamous cell carcinoma lines may be related to the mechanism of promoting apoptosis,blocking cell cycle at S phase and activation of AMPK-mTOR signal pathway.

Key words: metformin, cervical squamous cell carcinoma cell lines, cell cycle, apoptosis, mammalian target of rapamycin