Huang Wei, Yu Li-Fen, Zhong Jie, Qiao Min-Min, Jiang Feng-Xiang, Du Fang, Tian Xiang-Long, Wu Yun-Lin
Department of Gastroenterology, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai, China.
Dig Dis Sci. 2008 Jan;53(1):163-8. doi: 10.1007/s10620-007-9838-9. Epub 2007 May 8.
Angiotensin II (Ang II), a main effector peptide in the renin-angiotensin system, acts as a growth-promoting and angiogenic factor via angiotensin II receptor1 (AT1R). In this study, we investigated the expression of angiotensin II type1 receptor (AT1R) in gastric cancer and the effects of Ang II on the expression of MMP2 and MMP9 in the human gastric cancer cell line MKN-28 cells. The expression of the Ang II type I receptor was examined by western and immunocytochemistry in gastric cancer cell lines and detected by real-time PCR and immunohistochemistry in normal and gastric cancer tissues. The expression of MMP2 and MMP9 were detected by real-time PCR and western after treatment with Ang II and/or AT1R antagonist. AT1R were expressed in all human gastric cancer lines and the expression of AT1R was significantly higher in cancer tissues than that in normal gastric tissues (P < 0.01). Furthermore, Ang II promoted the expression of MMP2 and MMP9 in MKN-28 cells, and the stimulatory effects of Ang II could be blocked by AT1R antagonist. These results suggest that AT1R is involved in the progression of gastric cancer and may promote the angiogenesis of gastric cancer cell line (MKN-28), and these effects may be associated with the upregulation of MMP2 and MMP9.
血管紧张素II(Ang II)是肾素-血管紧张素系统中的一种主要效应肽,它通过血管紧张素II受体1(AT1R)发挥促生长和血管生成因子的作用。在本研究中,我们调查了血管紧张素II 1型受体(AT1R)在胃癌中的表达,以及Ang II对人胃癌细胞系MKN-28细胞中MMP2和MMP9表达的影响。通过蛋白质印迹法和免疫细胞化学检测胃癌细胞系中Ang II 1型受体的表达,并通过实时荧光定量PCR和免疫组织化学检测正常和胃癌组织中的表达。在用Ang II和/或AT1R拮抗剂处理后,通过实时荧光定量PCR和蛋白质印迹法检测MMP2和MMP9的表达。AT1R在所有人类胃癌细胞系中均有表达,且其在癌组织中的表达显著高于正常胃组织(P < 0.01)。此外,Ang II促进了MKN-28细胞中MMP2和MMP9的表达,而Ang II的刺激作用可被AT1R拮抗剂阻断。这些结果表明,AT1R参与了胃癌的进展,并可能促进胃癌细胞系(MKN-28)的血管生成,且这些作用可能与MMP2和MMP9的上调有关。