Antitumor effect of metformin on cholangiocarcinoma : In vitro and in vivo studies

( 最大 2000 件 )
URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28737
タイトル
Antitumor effect of metformin on cholangiocarcinoma : In vitro and in vivo studies
ファイル
内容記述

Abstract

Cholangiocarcinoma (CCA) is the most common biliary malignancy and the second most common hepatic malignancy after hepatocellular carcinoma (HCC). Treatment with the anti-diabetic drug metformin has been associated with reduced cancer incidence in patients with type 2 diabetes. Thus, the present study evaluated the effects of metformin on human CCA cell proliferation in vitro and in vivo and identified the microRNAs associated with its antitumor effects. Metformin inhibited the proliferation of the CCA cell lines HuCCT-1 and TFK-1 and blocked the G0 to G1 cell cycle transition, accompanied by AMP kinase pathway activation. Metformin treatment also led to marked decreases in cyclin D1 and cyclin-dependent kinase (Cdk) 4 protein levels and retinoblastoma protein phosphorylation. However, this drug did not affect p27kip protein expression. In addition, it reduced the phosphorylation of Axl, EphA10, ALK and PYK, as well as tumor proliferation in athymic nude mice with xenograft tumors. Furthermore, it markedly altered microRNA expression. These findings suggest that metformin may have clinical use in the treatment of CCA.

(医博甲619)

掲載誌
Oncology Reports
掲載誌(別表記)
Oncol Rep.
34
6
開始ページ
2987
終了ページ
2996
出版者
Spandidos Publications
出版年月日
2015-09-17
ISSN
1021-335X
NCID
AA11016405
PMID
26398221
DOI
10.3892/or.2015.4284
資料タイプ
学位論文
言語
英語
関連情報URL
https://doi.org/10.3892/or.2015.4284
権利関係
Copyright © Spandidos Publications 20195
"This is the Publisher's version of the following article: Antitumor effect of metformin on cholangiocarcinoma : In vitro and in vivo studies; Oncology Reports;  Volume 34 Issue 6 (2015) Pages: 2987-2996; doi:10.3892/or.2015.4284, which has been published in final form at https://doi.org/10.3892/or.2015.4284 . "
Publisher's Version: https://doi.org/10.3892/or.2015.4284
博士論文(全文を含む)
学位授与番号
博甲第619号
学位授与年月日
2015-12-25
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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