阿帕替尼通过阻断VEGF通路增强胃癌放疗疗效  

Apatinib increases radiosensitivity of gastric cancer by inhibiting VEGF pathway

作　　者：李彤[1] 翟二涛[1] 许丽霞[1] 黄霖琳 彭穗[1] 曾志荣[1] 

机构地区：[1]中山大学附属第一医院消化内科,广东广州510080

出　　处：《中国病理生理杂志》2017年第5期776-781,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81502079);广州市科技计划项目(No.201607010074)

摘　　要：目的:探讨血管内皮生长因子(VEGF)受体2酪氨酸激酶抑制剂阿帕替尼对胃癌细胞株SGC-7901放疗疗效的影响及其可能机制。方法:试验设对照组、阿帕替尼组、单纯放疗组与联合组。CCK-8法检测细胞活力,流式细胞术分析细胞凋亡比例与细胞周期,免疫荧光染色观察细胞核内γ-H_2AX的表达,Western blot法检测细胞增殖和凋亡相关蛋白。结果:与阿帕替尼组或单纯放疗组相比,阿帕替尼联合X射线显著降低SGC-7901细胞的生长活力(P<0.01),增殖相关蛋白p-PLCγ1和p-ERK1/2的水平下降;细胞凋亡比例明显升高(P<0.01),凋亡相关蛋白PARP、cleaved caspase-9和cleaved caspase-3蛋白水平上调,Bcl-2表达下降;SGC-7901细胞核内γ-H_2AX焦点淬灭延迟,表明阿帕替尼干扰放射线诱导的DNA双链断裂的修复;SGC-7901 G_2期细胞比例显著增高(P<0.01)。结论:阿帕替尼通过阻断VEGF通路增加胃癌细胞对X射线照射的敏感性。AIM：To investigate radiosensitization effect of apatinib, a vascular endothelial growth factor （VEGF） receptor2 tyrosine kinase inhibitor, on human gastric carcinoma cell line SGC-7901 and its mechanism.METHODS： SGC-7901 cells were divided into control group, apatinib group, radiotherapy group and combination group. The cell viability was measured by CCK-8 assay. The changes of cell apoptosis and cell cycle were analyzed by flow cytometry. The protein levels of cell apoptosis biomarkers, such as PARP, cleaved caspase-9, cleaved caspase-3 and Bcl-2, and cell proliferation biomarkers, p-PLCγ1 and p-ERK1/2, were detected by Western blot. γ-H2AX expression was detected by immunofluorescence.RESULTS： Compared with apatinib group and radiation group, the cell viability was inhibited after treatment with both apatinib and X-ray （P〈0.01）. The protein levels of cell proliferation markers p-PLCγ1 and p-ERK1/2 were down-regulated. The cell apoptosis was enhanced （P〈0.01）. The protein levels of cell apoptosis makers such as PARP, cleaved caspase-9 and cleaved caspase-3 were up-regulated, while Bcl-2 was down-regulated. The disappearance of γ-H2AX foci in the nucleus was delayed, indicating that apatinib impaired the repair of radiation-induced DNA double-strand breaks. The proportion of G2 phase was significantly increased （P〈0.01）. The combination treatment had more significant effect on SGC-7901 cells than treating with apatinib or radiotherapy alone.CONCLUSION： Apatinib increases the radiosensitivity of gastric cancer cells via blocking VEGF pathway.

关 键 词：胃癌 放疗 阿帕替尼 血管内皮生长因子 

分 类 号：R730.23[医药卫生—肿瘤] R735.2[医药卫生—临床医学]