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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3719

Title: Angiotensin receptor blockade attenuates cholangiocarcinoma cell growth by inhibiting the oncogenic activity of Yes-associated protein.
Other Titles: アンギオテンシン受容体を遮断することによりYes関連蛋白質の発癌活性が阻害されて胆管癌細胞増殖が抑制される
Authors: Saikawa, Soichiro
Kaji, Kosuke
Nishimura, Norihisa
Seki, Kenichiro
Sato, Shinya
Nakanishi, Keisuke
Kitagawa, Koh
Kawaratani, Hideto
Kitade, Mitsuteru
Moriya, Kei
Namisaki, Tadashi
Mitoro, Akira
Yoshiji, Hitoshi
Keywords: Angiotensin receptor blocker
Yes-associated protein
G protein-coupled receptor
Issue Date: 10-Oct-2018
Publisher: Elsevier
Citation: Cancer letters Vol.434 p.120-129 (2018 Oct)
Abstract: Cholangiocarcinoma (CCA) is a destructive malignancy with limited responsiveness to conventional chemotherapy. Although angiotensin receptor blockers (ARBs) have gained attention for their potential anticancer activity, little is known about their effects on CCA. The transcriptional co-activator, Yes-associated protein (YAP) is a critical oncogene in several cancers, including CCA. Following recent evidence showing that YAP is regulated by angiotensin II (AT-II), we investigated the effects of an ARB, losartan, on two human CCA cell lines (KKU-M213 and HuCCT-1) with regards to YAP oncogenic regulation. Losartan suppressed AT-II-induced CCA cell proliferation in a dose-dependent manner, induced apoptosis, decreased YAP (Ser127), and downregulated the YAP target genes CTGF, CYR61, ANKRD1, and MFAP5. However, losartan did not affect epithelial-mesenchymal transition, differentiation, or stemness in the CCA cells. Xenograft tumor growth assay showed that oral administration of a low clinical dose of losartan considerably reduced subcutaneous tumor burden and attenuated intratumor vascularization in CCA cell-derived xenograft tumors in BALB/c nude mice. These results indicate that ARB therapy could serve as a potential novel strategy for CCA treatment.
Description: 博士(医学)・甲第728号・令和2年3月16日
Copyright © 2018 Elsevier B.V. All rights reserved.
URI: http://hdl.handle.net/10564/3719
ISSN: 03043835
Academic Degrees and number: 24601A728
Degree-granting date: 2020-03-16
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2019年度

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