血管紧张素Ⅱ通过AT1R/ERK/MAPK信号通路影响乳腺癌细胞MCF-7的增殖能力  

The effects of angiotensin Ⅱ on the proliferation in human breast cancer cell line MCF-7 through AT1R/ERK/MAPK pathway

作　　者：钟小红[1,2] 吴晓安[2] 胡冰[1] 

机构地区：[1]安徽医科大学附属省立医院肿瘤内科,安徽合肥230001 [2]解放军第174医院肿瘤内科,福建厦门361003

出　　处：《中国癌症杂志》2014年第9期652-656,共5页China Oncology

摘　　要：背景与目的:研究表明,肾素-血管紧张素系统(renin-angiotensin system,RAS)与肿瘤发生、发展密切有关,血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)是RAS系统最重要的组成部分。本文旨在探讨AngⅡ对乳腺癌细胞株MCF-7细胞增殖的作用及其机理。方法:采用CCK8法观察AngⅡ对MCF-7细胞增殖的影响、氯沙坦(AT1R抑制剂)及PD98059(MAPK抑制剂)对AngⅡ介导MCF-7细胞增殖变化的影响;利用蛋白质印迹法(Western blot)检测不同浓度AngⅡ处理MCF-7细胞后ERK及p-ERK1/2蛋白的表达变化。结果:AngⅡ具有明显的促MCF-7细胞增殖作用,并呈时间和剂量依赖性,分别在24 h时和10-7 mol/L浓度处理时促进作用最为显著(P<0.000 1);氯沙坦能显著降低AngⅡ促进细胞增殖的作用(P=0.022);Western blot检测结果显示,AngⅡ能激活p-ERK蛋白的表达水平;进一步用MAPK抑制剂PD98059处理能够部分逆转AngⅡ的促细胞增殖作用。结论:AngⅡ通过激活AT1R/ERK信号通路增强乳腺癌细胞MCF-7的增殖能力,使用AT1R抑制剂或MAPK抑制剂均能抑制AngⅡ的作用。因此,靶向AngⅡ/AT1R/MAPK可能为乳腺癌治疗提供新的途径。Background and purpose：Studies have shown that renin-angiotensin system （RAS） is closely associated with tumor progress. angiotensinⅡ （AngⅡ） is the most important component of RAS. This study aimed to investigate the possible mechanism by which AngⅡ affected the cell proliferation in human breast cancer cell line MCF-7.Methods：CCK-8 was used to investigate the cell proliferation alteration of MCF-7 cells after treatment of AngⅡ at different dose and time. The inlfuence of losartan （an AT1R inhibitor） and PD98059 （a MAPK inhibitor） in AngⅡ-enhanced cell proliferation was detected by CCK-8. Protein expression was analyzed by Western blot.Results：AngⅡ stimulated the growth of breast cancer cells in a dose- and time-dependent manner. The maximal proliferation effect on MCF-7 cells was obtained with 10-7 mol/L AngⅡ and 24 h, respectively （P〈0.000 1）. Losartan signiifcantly decreased the level of AngⅡ-induced proliferative effects （P〈0.05）. Western blot showed that AngⅡ caused rapid activation of p-ERK. In addition, PD98059 could signiifcantly suppress AngⅡ-promoted cell proliferation.Conclusion：AngⅡ can promote MCF-7 cell proliferation through AT1R/ERK/MAPK pathway activation, which could be reversed by losartan or PD98059. Therefore, targeting AngⅡ/AT1R/MAPK signaling could be a novel therapeutic for breast cancer.

关 键 词：乳腺癌 血管紧张素Ⅱ ERK1/2 细胞增殖 AT1R 

分 类 号：R737.9[医药卫生—肿瘤]