阿帕替尼对胃癌HGC-27细胞放射敏感性的影响及其作用机制

目的 探讨阿帕替尼对胃癌HGC-27细胞放射敏感性的影响及可能的作用机制。方法 以不同浓度阿帕替尼（5 μmol/L、10 μmol/L、15 μmol/L、20 μmol/L）以及不同照射剂量（2 Gy、4 Gy、6 Gy、10 Gy、20 Gy）分别处理HGC-27细胞，再选取2 Gy和6 Gy单独照射或联合10 μmol/L阿帕替尼处理HGC-27细胞；采用ELISA法检测细胞中血管内皮生长因子（vascular endothelial growth factor，VEGF）的表达情况，CCK-8法检测细胞增殖能力，流式细胞术检测细胞凋亡和细胞周期，免疫荧光染色技术检测γ-H2AX的表达情况。结果 阿帕替尼呈浓度及时间依赖性抑制胃癌HGC-27细胞增殖（均P<0.05）；不同剂量照射可促进细胞VEGF表达释放，且呈时间及剂量依赖性（均P<0.01）。10 μmol/L阿帕替尼分别联合2 Gy和6 Gy照射后，HGC-27细胞增殖抑制作用、细胞凋亡率及G2/M期的细胞比例均较单照组升高（均P<0.01），且6 Gy联合组的作用强度大于2 Gy联合组（均P<0.01）。6 Gy联合组细胞核内γ-H2AX焦点淬灭较6 Gy单照组延迟。结论 阿帕替尼通过抑制细胞增殖，促进细胞凋亡并诱导细胞周期再分布增强胃癌HGC-27细胞放射敏感性，其作用机制可能与延迟γ-H2AX表达而干扰DNA双链断裂修复有关。

Effect of Apatinib on radiosensitivity of gastric cancer HGC?27 cells and its mechanism

 Objective To investigate the effect of Apatinib on the radiosensitivity of gastric cancer HGC-27 cells and its possible mechanism. Methods HGC-27 cells were treated with different concentrations of Apatinib (5 μmol/L, 10 μmol/L, 15 μmol/L, 20 μmol/L) and different irradiation doses (2 Gy, 4 Gy, 6 Gy, 10 Gy, 20 Gy). HGC-27 cells were then irradiated with 2 Gy and 6 Gy alone or combined with 10 μmol/L Apatinib. The expression of vascular endothelial growth factor （VEGF） was detected by ELISA, cell proli-feration capacity was detected by CCK-8, cell apoptosis and cell cycle were detected by flow cytometry, and expression of γ-H2AX was detected by immunofluorescence staining. Results Apatinib inhibited the proliferation of gastric cancer HGC-27 cells in a concentration- and time-dependent manner (all P<0.05). Different doses of irradiation promoted the release of VEGF in a time-and dose-dependent manner (all P<0.01). After the combination of 10 μmol/L Apatinib with 2 Gy and 6 Gy irradiation, respectively, the inhibition of cell proliferation, apoptosis rate and proportion of cells in G2/M phase of HGC-27 cells were increased compared with those in the single irradia-tion group (all P<0.01). The effect intensity of 6 Gy combined group was greater than that of 2 Gy combined group (all P<0.01). The nucleus focal quenching of γ-H2AX in the 6 Gy combined group was delayed compared with that in the 6 Gy single irradiation group. Conclusions Apatinib enhances the radiosensitivity of gastric cancer HGC-27 cells by inhibiting cell proliferation, promoting cell apoptosis and inducing cell cycle redistribution. The underlying mechanism may be related to the delay of γ-H2AX expression and the interference of DNA double-strand fracture repair.