CAJ | 학술논문

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(angiotensin Ⅱ，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<0.0001)；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。
배경여목적：연구표명，신소-혈관긴장소계통(renin-angiotensin system，RAS)여종류발생、발전밀절유관，혈관긴장소Ⅱ(angiotensin Ⅱ，AngⅡ)시RAS계통최중요적조성부분。본문지재탐토AngⅡ대유선암세포주MCF-7세포증식적작용급기궤리。방법：채용CCK8법관찰AngⅡ대MCF-7세포증식적영향、록사탄(AT1R억제제)급PD98059(MAPK억제제)대AngⅡ개도MCF-7세포증식변화적영향；이용단백질인적법(Western blot)검측불동농도AngⅡ처리MCF-7세포후ERK급p-ERK1/2단백적표체변화。결과：AngⅡ구유명현적촉MCF-7세포증식작용，병정시간화제량의뢰성，분별재24 h시화10-7 mol/L농도처리시촉진작용최위현저(P<0.0001)；록사탄능현저강저AngⅡ촉진세포증식적작용(P=0.022)；Western blot검측결과현시，AngⅡ능격활p-ERK단백적표체수평；진일보용MAPK억제제PD98059처리능구부분역전AngⅡ적촉세포증식작용。결론：AngⅡ통과격활AT1R/ERK신호통로증강유선암세포MCF-7적증식능력，사용AT1R억제제혹MAPK억제제균능억제AngⅡ적작용。인차，파향AngⅡ/AT1R/MAPK가능위유선암치료제공신적도경。
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.