Abstract 892: Angiotensin II /angiotensin II type I receptor (AGTR1) promotes cell growth in epithelial ovarian cancer

Abstract

Abstract Background: Angiotensin and its receptor, AGTR (Anigiotensin receptor) are known as main effectors molecules of renin-angiotensin system in regulating the physiological processes of the cardiovascular system. Not only do they function as an endocrine system, but they have recently reported to regulate cell proliferation, angiogenesis, invasiveness, and viabilities via inducing intercellular signaling pathways. The aim of this study is to evaluate the role of angiotensin II and AGTR1 on cell survival and proliferation in epithelial ovarian carcinoma cells. Methods: Expressions of AGTR1 were evaluated by immunohistochemistry in epithelial ovarian carcinoma tissues and analyzed the correlation between AGTR1 expression and clinicopathological characteristics of patients. For in vitro test, we checked the level of expression for angiotensin II and AGTR1 in human ovarian cancer cell lines by Western blot. A recombinant angiotensin II and its blocker losartan were treated into the cells. For cell viabilities and proliferations were estimated by MTT assay. Results: Through checking the expression of AGTR1 in human ovarian cancer cells, we selected A2780 and HeyA8 cells for in vitro tests because these cells have relatively high expression. Exogenous treatment of angiotensin II resulted in increased cell growth of both cells. Losartan, specific blocker of AGTR1, diminished the angiotensin II-induced increased cell growth. Moreover, we identified that angiotensin II activated Akt and STAT signaling through AGTR1 and pretreatment of losartan inhibited those activations. Conclusion: In this study, we inquired into the role of angiotensin II-AGTR1 interaction in ovarian cancer. They positively regulate cell survivability and proliferation and activate intercellular signaling involving Akt and STAT via suggesting their oncogenic mechanisms. Moreover, treatment of losartan, showed antiproliferative effect by inhibiting the activations of AGTR1 mediated signaling. These results suggest that AGTR1 inhibitor like as losartan could be a novel therapeutic strategy treating this cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 892. doi:1538-7445.AM2012-892