Mechanism of gemcitabine-induced suppression of human cholangiocellular carcinoma cell growth

( 最大 2000 件 )
URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28736
タイトル
Mechanism of gemcitabine-induced suppression of human cholangiocellular carcinoma cell growth
ファイル
内容記述

Abstract

Although gemcitabine (2',2'-difluorocytidine monohydrochloride) is a common anticancer agent of cholangiocellular carcinoma (CCC), its growth inhibitory effects and gemcitabine resistance in CCC cells are poorly understood. Our aims were to uncover the mechanism underlying the antitumor effect of gemcitabine and to analyze the mechanism regulating in vitro CCC cell gemcitabine resistance. In addition, we sought to identify miRNAs associated with the antitumor effects of gemcitabine in CCCs. Using a cell proliferation assay and flow cytometry, we examined the ability of gemcitabine to inhibit cell proliferation in three types of human CCC cell lines (HuCCT-1, Huh28, TKKK). We also employed western blotting to investigate the effects of gemcitabine on cell cycle-related molecules in CCC cells. In addition, we used array chips to assess gemcitabine-mediated changes in angiogenic molecules and activated tyrosine kinase receptors in CCC cells. We used miRNA array chips to comprehensively analyze gemcitabine-induced miRNAs and examined clusters of differentially expressed miRNAs in cells with and without gemcitabine treatment. Gemcitabine inhibited cell proliferation in a dose- and time-dependent manner in HuCCT-1 cells, whereas cell proliferation was unchanged in Huh28 and TKKK cells. Gemcitabine inhibited cell cycle progression in HuCCT-1 cells from G0/G1 to S phase, resulting in G1 cell cycle arrest due to the reduction of cyclin D1 expression. In addition, gemcitabine upregulated the angiogenic molecules IL-6, IL-8, ENA-78 and MCP-1. In TKKK cells, by contrast, gemcitabine did not arrest the cell cycle or modify angiogenic molecules. Furthermore, in gemcitabine-sensitive HuCCT-1 cells, gemcitabine markedly altered miRNA expression. The miRNAs and angiogenic molecules altered by gemcitabine contribute to the inhibition of tumor growth in vitro.

(医博甲618)

著者
著者 豊田 由花
著者(ヨミ) トヨタ ユカ
著者(別表記) Toyota Yuka
掲載誌
International Journal of Oncology
掲載誌(別表記)
Int J Oncol.
47
4
開始ページ
1293
終了ページ
1302
出版者
Spandidos Publications
出版年月日
2015-08-07
ISSN
1019-6439
NCID
AA10992511
PMID
26252371
DOI
10.3892/ijo.2015.3118
資料タイプ
学位論文
言語
英語
関連情報URL
https://doi.org/10.3892/ijo.2015.3118
権利関係
Copyright © Spandidos Publications 2015.
"This is the Publisher's version of the following article: Mechanism of gemcitabine-induced suppression of human cholangiocellular carcinoma cell growth; International Journal of Oncology; Volume 47 Issue 4 (2015) Pages: 1293-1302; doi: 10.3892/ijo.2015.3118, which has been published in final form at https://doi.org/10.3892/ijo.2015.3118 . "
Publisher's Version with DOI: https://doi.org/10.3892/ijo.2015.3118
博士論文(全文を含む)
学位授与番号
博甲第618号
学位授与年月日
2015-09-29
学位名
博士(医学)
学位授与機関
香川大学
区分
香川大学
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