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

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28736
Title
Mechanism of gemcitabine-induced suppression of human cholangiocellular carcinoma cell growth
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Description

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)

Author
著者 豊田 由花
著者(ヨミ) トヨタ ユカ
著者(別表記) Toyota Yuka
Publication Title
International Journal of Oncology
Publication Title Alternative
Int J Oncol.
Volume
47
Issue
4
Start Page
1293
End Page
1302
Publisher
Spandidos Publications
Published Date
2015-08-07
ISSN
1019-6439
NCID
AA10992511
PMID
26252371
DOI
10.3892/ijo.2015.3118
Resource Type
Thesis or Dissertation
Language
eng
Resource URL
https://doi.org/10.3892/ijo.2015.3118
Rights
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
Text Version
ETD
Grant ID
博甲第618号
Grant Date
2015-09-29
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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