目的：探讨金雀异黄素对肝癌Bel-7404细胞的放疗增敏作用及其作用机制。方法：将肝癌Bel-7404细胞分为正常对照组(NC)、Gen处理组(G)、单纯照射组(R)及Gen+辐照组(G+R)。除NC组外，其余各组分别采用5 μmol/L Gen和/或8 Gy X射线（剂量率300 cGy/min）处理，利用CCK-8 法、流式细胞术分别检测Gen与X射线单独或联用对Bel-7404细胞的增殖、细胞周期和凋亡的影响；并通过Western blotting检测对ATM-Chk2通路相关蛋白表达及其磷酸化水平的影响。结果： G+R组细胞在处理后24 h时细胞增殖抑制率即显著高于R组\[（16.80±2.59）% vs（9.76±2.11）%，P<0.05\]，且随着时间的延长，对细胞增殖的抑制作用更明显；与NC组比较，G、R、G+R组细胞凋亡率和G2/M期细胞比例均显著增加（P<005或P<0.01），且G+R组凋亡率显著高于R组\[（51.86±2.88）% vs （33.18±4.48）%，P<0.01\]；G+R组中p-ATM与p-Chk2表达量明显高于G组、R组和NC组。结论： Gen可以增强肝癌Bel-7404细胞的放疗敏感性，其机制可能与ATM-Chk2信号通路的激活有关。

Objective:To investigate the effects and mechanisms of genistein (Gen) enhancing radio-sensitivity of Hepatoma Bel-7404 cells. Methods: Bel-7404 cells were divided into four groups: normal control (NC), genistein treatment (G), radiation alone treatment (R) as well as genistein+radiation treatment group (G+R). Except the NC group, the other three groups were treated with genistein (5 μmol/L) and/or X-ray irradiation (8 Gy) at a dose rate of 300 cGy/min, respectively. The effect of Gen and x-ray on cell proliferation, cell cycle and apoptosis of Bel-7404 cells were detected using CCK-8 and flow cytometry, respectively; the expression levels of ATM-Chk2 signal pathway related proteins were detected using Western blotting.Results:The inhibitory rate on cell proliferation in G+R group was significantly higher than that in R group at 24 h after irradiation (\[16.80±2.59\]% vs \[9.76±2.11\]%, P<0.05). And the inhibitory effect was enhanced in a time-dependent manner. Compared with NC group, the cell apoptosis rate and percentage of cells in G2/M phase were all significantly increased in G, R and G+R group (P<0.05 or P<0.01). Combination of Gen with X-ray further increased cell apoptosis compared with X-ray treatment alone group (\[51.86±288\]% vs \[33.18±4.48\]%, P<0.01). Furthermore, the expressions of p-ATM and p-Chk2 were obviously up-regulated in G+R group compared with that of R, G and NC group. Conclusions: Gen could enhance radiosensitivity of hepatoma Bel-7404 cells, and the mechanism might be related with the activation of ATM-Chk2 signal pathway.

国家自然科学基金资助项目（No. 31570869,31170844）