目的:探讨低剂量二甲双胍对肝癌Hep-G2细胞荷瘤小鼠的放疗增敏作用及其机制。方法:2017年9月至2019年1月，滨州医学院附属滨州市中心医院建立Hep-G2细胞荷瘤小鼠模型，分为对照组、单独放射治疗组(放疗组)、低剂量二甲双胍组(二甲双胍组)及低剂量二甲双胍联合放射治疗组(联合治疗组)。经不同治疗后，记录各组小鼠瘤体生长情况，计算肿瘤三倍倍增时间(Tripling time，TT)、肿瘤生长延缓时间(Tumor growth delay，TGD)以及增敏系数(Enhancement Factor，EF)。治疗21 d后处死小鼠，剥瘤称重，并计算各组抑瘤率；流式细胞仪检测不同治疗对细胞周期和凋亡的影响；免疫印迹技术检测不同治疗对STAT3信号通路及凋亡相关蛋白表达的影响。结果:低浓度二甲双胍联合放疗可以显著抑制小鼠荷瘤的生长，具有较好的放射增敏作用，其增敏系数为1.52；联合治疗组可以显著引起Hep-G2细胞G2/M期阻滞并诱导凋亡[联合治疗组比放疗组：G2/M期比例，(28.4±5.3)%比(10.8±3.7)%，χn 2＝8.55，n P<0.05；细胞凋亡率，(40.8±7.7)%比(29.5±5.9)%，χn 2＝11.83，n P<0.01]；与放疗组比较，联合治疗组能够显著降低STAT3的磷酸化水平(n t＝10.71，n P<0.01)，并参与调控凋亡相关蛋白的表达。n 结论:二甲双胍对肝癌Hep-G2荷瘤小鼠具有较高的抑瘤和放射增敏作用，其增敏机制可能与诱导肿瘤细胞G2/M期阻滞，抑制STAT3信号通路有关。“,”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)%, n t=8.55, n P<0.05; apoptosis rate, (28.4±5.3)% vs.(10.8±3.7)%,n t=11.83, n P<0.01]. Furthermore, compared with the single radiotherapy group, the combined group could significantly reduce the phosphorylation level of STAT3 (n t=10.71, n P<0.01), and regulate the expression of apoptosis-related proteins.n 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.