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

( Max 2000 Items )
URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28451
Title
Angiotensin receptor blocker telmisartan inhibits cell proliferation and tumor growth of cholangiocarcinoma through cell cycle arrest
File
Description

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)

Author
著者 寒川 英里
著者(ヨミ) サムカワ エリ
著者(別表記) Samukawa Eri
Publication Title
International Journal of Oncology
Publication Title Alternative
Int J Oncol.
Volume
51
Issue
6
Start Page
1674
End Page
1684
Publisher
Spandidos Publications
Published Date
2017-10-23
ISSN
1019-6439
NCID
AA10992511
PMID
29075786
DOI
10.3892/ijo.2017.4177
Resource Type
Thesis or Dissertation
Language
eng
Relation
PMCID: PMC5673010
出版社版DOIリンク(URL):https://doi.org/10.3892/ijo.2017.4177
Resource URL
https://doi.org/10.3892/ijo.2017.4177
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673010/
Rights
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
Text Version
ETD
Grant ID
博甲第680号
Grant Date
2018-03-24
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
Copyright (C) 2009 Kagawa University All rights reserved.