RESUMEN
Objective:To investigate the radiosensitization effect and mechanism of low dose metformin on Hep-G2 tumor bearing mice.Methods:All mice were divided into four groups: control group, radiotherapy group, metformin treatment group and metformin combined with radiotherapy group.After different treatments, the tumor volume of mice in each group was recorded, and the tripling time (TT), tumor growth delay (TGD) and enhancement factor (EF) were calculated.After 21 days, all mice were killed, stripped and weighed, and the tumor inhibition rate was calculated.The effects of different treatments on cell cycle and apoptosis were detected by flow cytometry, and the influences of different treatments on STAT3 signaling pathway and apoptosis related protein expression were detected by immunoblotting.Results:Low dose metformin combined with radiotherapy could significantly inhibit the growth of tumor in mice, and had a better radiosensitization effect, with a sensitization coefficient of 1.52.In addition, the combined treatment group could significantly induce G2/M arrest and apoptosis of Hep-G2 cells[the combined group vs.The radiotherapy group: G2/M phase ratio, (28.4±5.3)% vs.(10.8±3.7)%, t=8.55, P<0.05; apoptosis rate, (28.4±5.3)% vs.(10.8±3.7)%, t=11.83, P<0.01]. Furthermore, compared with the single radiotherapy group, the combined group could significantly reduce the phosphorylation level of STAT3 ( t=10.71, P<0.01), and regulate the expression of apoptosis-related proteins. Conclusion:Metformin has antitumor and radiosensitizing effects on Hep-G2 hepatoma-bearing mice, the mechanism of which may be related to the induction of G2/M phase arrest and the inhibition of STAT3 signaling pathway.