血管紧张素Ⅱ受体1在人胃癌细胞中的表达及其拮抗剂对胃癌荷瘤裸鼠生长的抑制作用

Expression of the angiotensin Ⅱ type1 receptor in human gastric cancer cells and its antagonist inhibitory effect on growth of xenograft with gastric cancer

目的:检测血管紧张素Ⅱ受体1(AT1R)在人胃癌细胞株中的表达及其拮抗剂对人胃癌荷瘤裸鼠生长的抑制作用。方法:采用实时定量PCR和蛋白印迹分析法检测AT1R在胃癌细胞株中的表达。建立人胃癌裸鼠移植瘤模型,分别以2mg/kg和5mg/kgTCV-116(AT1R拮抗剂)每日给荷瘤裸鼠灌胃,观察肿瘤体积的变化并绘制肿瘤生长曲线;以免疫组织化学染色观察胃癌裸鼠移植瘤的微血管密度(MVD)和血管内皮生长因子(VEGF)表达。结果:AT1R在人胃癌细胞株中有较高水平的表达。经TCV-116处理的胃癌荷瘤裸鼠移植瘤体积较对照组显著减小,且TCV-116处理组的MVD和VEGF表达水平也较对照组显著降低。结论:选择性AT1R拮抗剂对人胃癌裸鼠移植瘤的生长具抑制作用,其可能是通过抑制肿瘤血管生成的途径产生抑制作用;故阻断血管紧张素Ⅱ(AngⅡ)可能是治疗胃癌的一种新方法。

Objective To investigate the expression of angiotensin Ⅱ（AngⅡ） type1 receptor （AT1R） in human gastric cancer cell lines and the inhibitory effect of AT1R antagonist on growth of gastric cancer xenograft in nude mice. Methods The expression of AT1R was analyzed by real-time PCR and Western blotting in four gastric cancer cell lines（MKN-28, SGC-7901, MKN-45 and AGS）. Thirty nude mice models with tumor xenograft were prepared. The mice were given AT1R antagonist TCV-116 daily by gavage（2 mg/kg and 5 mg/kg respectively）. The growth of xenografts were observed. Microvessel density （MVD） and expression of vascular endothelial growth factor （VEGF） were assessed by immunohistochemistry. Results Both the expression level of mRNA and protein of AT1R were higher in the four human gastric cancer cell lines. The growth of xenografts was significantly suppressed by treatment with TCV-116. MVD and VEGF expression were significantly suppressed after TCV-116 treatment as well. Conclusions A selective antagonist of AT1R had inhibitory effect on the growth of human gastric cancer xenograft by suppressing the angiogenesis of tumor. The blockade of AngⅡ might be a noteworthy anticancer therapeutic option in gastric cancer.