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Cited 28 time in webofscience Cited 29 time in scopus
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Dual targeting of angiotensin receptors (AGTR1 and AGTR2) in epithelial ovarian carcinoma

Authors
Park, Young-AeChoi, Chel HunDo, In-GuSong, Sang YongLee, Jae KwanCho, Young JaeChoi, Jung-JooJeon, Hye KyungRyu, Ji YoonLee, Yoo-YoungKim, Tae-JoongBae, Duk-SooLee, Jeong-WonKim, Byoung-Gie
Issue Date
Oct-2014
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Keywords
AGTR1; AGTR2; Losartan; CGP42112A; Ovarian carcinoma
Citation
GYNECOLOGIC ONCOLOGY, v.135, no.1, pp 108 - 117
Pages
10
Indexed
SCI
SCIE
SCOPUS
Journal Title
GYNECOLOGIC ONCOLOGY
Volume
135
Number
1
Start Page
108
End Page
117
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/8913
DOI
10.1016/j.ygyno.2014.06.031
ISSN
0090-8258
1095-6859
Abstract
Objective. The renin-angiotensin system (RAS) influences cardiovascular homeostasis, and Angiotensin II type 1 receptor (AGTR1) is the main effector of RAS, and AGTR2 antagonizes AGTR1. Accumulating evidence supports the role of RAS in the paracrine regulation of tumorigenesis in several cancer types. Although treatment with AGTR1 antagonist (losartan) or AGTR2 agonist (CGP42112A) inhibits tumor progression in several cancer cells, their combined treatment has not been reported. Methods. In this study, we estimated the expression of AGTR1 and AGTR2 in epithelial ovarian cancer cells and tissues. Then, we evaluated the anti-cancer effects of combined treatment with losartan and/or CGP42112A in ovarian cancer cells and human umbilical vein endothelial cells (HUVEC). Results. AGTR1 protein was detected in 86% of ovarian cancer tissues, while AGTR2 was not detected in immunohistochemistry. The mRNA expression of AGTR1 obtained from the cancer genome atlas (TCGA) dataset showed that AGTR1 overexpression was correlated with poor survival. Treatment with either losartan or CGP42112A reduced the angiotensin II (Ang II)-mediated cell survival in both ovarian cancer cells and HUVEC. Combined treatment with losartan and CGP42112A synergistically decreased cell survival. As a downstream pathway, phosphorylation of phospholipase C beta 3 (PLC beta 3) and expression of vascular endothelial growth factor (VEGF) decreased synergistically in combined treatment. Conclusion. The results suggest that dual regulation of AGTR1 and AGTR2 may be a novel therapeutic strategy for epithelial ovarian carcinoma through inhibition of cancer cell survival as well as anti-angiogenesis. Translational relevance. This study investigated the expressions of AGTRI and AGTR2 in epithelial ovarian carcinoma and the therapeutic potential of AGTR modulation with specific antagonist and/or agonist in epithelial ovarian cancer cells. Treatment of AGTR1 antagonist, losartan and/or AGTR2 agonist, CGP42112A synergistically mediated anti-cancer effects including the decrease of cell survival and down-regulation of VEGF. (C) 2014 Elsevier Inc. All rights reserved.
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Lee, Jae Kwan
Guro Hospital (Department of Obstetrics and Gynecology, Guro Hospital)
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