阿帕替尼通过阻断VEGF通路增强胃癌放疗疗效

发布时间：2018-06-05 13:09

本文选题：胃癌 + 放疗　；参考：《中国病理生理杂志》2017年05期

【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(P0.01),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(P0.01),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(P0.01)。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。
[Abstract]:Aim: to investigate the effect of Apatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGF) receptor 2, on radiotherapy of gastric cancer cell line SGC-7901 and its possible mechanism. Methods: the cell viability was detected by CCK-8 method in the control group, apatinib group, radiotherapy group and combined group. The apoptosis rate and cell cycle were analyzed by flow cytometry. Immunofluorescence staining was used to detect the expression of 纬 -HSPI 2AX in the nucleus. Western blot assay was used to detect the cell proliferation and apoptosis related proteins. Results: compared with Apatinib group or radiotherapy alone group, Apatinib combined with X ray significantly decreased the growth activity of SGC-7901 cells and the levels of p-PLC 纬 1 and p-ERK1/2. The percentage of apoptosis increased significantly, and the levels of caspase-9 and cleaved caspase-3 proteins increased significantly. The expression of Bcl-2 decreased and the focal quenching of 纬 -H2AX in the nucleus of SGC-7901 was delayed. The results showed that the proportion of SGC-7901 G2 phase cells of DNA double strand breaks induced by Apatinib interference was significantly increased (P 0.01). Conclusion: Apatinib increased the sensitivity of gastric cancer cells to X-ray irradiation by blocking the VEGF pathway.
【作者单位】：中山大学附属第一医院消化内科;
【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)
【分类号】：R730.23;;R735.2

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