Angiotensin receptor blocker telmisartan inhibits cell proliferation and tumor growth of cholangiocarcinoma through cell cycle arrest

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28451
タイトル
Angiotensin receptor blocker telmisartan inhibits cell proliferation and tumor growth of cholangiocarcinoma through cell cycle arrest
ファイル
内容記述

Abstract

Cholangiocarcinoma (CCA) is at an advanced stage at the time of its diagnosis, and developing a more effective treatment of CCA would be desirable. Angiotensin II type 1 (AT1) receptor blocker (ARB), telmisartan may inhibit cancer cell proliferation, but the mechanisms by which telmisartan affects various cancers remain unknown. In this study, we evaluated the effects of telmisartan on human CCA cells and to assess the expression of microRNAs (miRNAs). We studied the effects of telmisartan on CCA cells using two cell lines, HuCCT-1 and TFK-1. In our experiments, telmisartan inhibited the proliferation of HuCCT-1 and TFK-1 cells. Additionally, telmisartan induced G0/G1 cell cycle arrest via blockade of the G0 to G1 cell cycle transition. Notably, telmisartan did not induce apoptosis in HuCCT-1 cells. This blockade was accompanied by a strong decrease in cell cycle-related protein, especially G1 cyclin, cyclin D1, and its catalytic subumits, Cdk4 and Cdk6. Telmisartan reduced the phosphorylation of EGFR (p-EGFR) and TIMP-1 by using p-RTK and angiogenesis array. Furthermore, miRNA expression was markedly altered by telmisartan in HuCCT-1. Telmisartan inhibits tumor growth in CCA xenograft model in vivo. In conclusion, telmisartan was shown to inhibit human CCA cell proliferation by inducing cell cycle arrest.

Keywords: cholangiocarcinoma, telmisartan, cell cycle, angiotensin II type 1 receptor blocker

(医博甲680)

著者
著者 寒川 英里
著者(ヨミ) サムカワ エリ
著者(別表記) Samukawa Eri
掲載誌
International Journal of Oncology
掲載誌(別表記)
Int J Oncol.
51
6
開始ページ
1674
終了ページ
1684
出版者
Spandidos Publications
出版年月日
2017-10-23
ISSN
1019-6439
NCID
AA10992511
PMID
29075786
DOI
10.3892/ijo.2017.4177
資料タイプ
学位論文
言語
英語
関連情報
PMCID: PMC5673010
出版社版DOIリンク(URL):https://doi.org/10.3892/ijo.2017.4177
関連情報URL
https://doi.org/10.3892/ijo.2017.4177
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673010/
権利関係
Copyright: © Samukawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
DOI: https://doi.org/10.3892/ijo.2017.4177
博士論文(全文を含む)
学位授与番号
博甲第680号
学位授与年月日
2018-03-24
学位名
博士(医学)
学位授与機関
香川大学
区分
香川大学
Copyright (C) 2009 Kagawa University All rights reserved.