关键词: 乳腺癌, 血管紧张素Ⅱ, AT1R, ERK1/2, 细胞增殖

Abstract:

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 influence 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 significantly 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 significantly 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.

Key words: Breast cancer, Angiotensin Ⅱ, AT1R, ERK1/2, Cell proliferation