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

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28737
Title
Antitumor effect of metformin on cholangiocarcinoma : In vitro and in vivo studies
File
Description

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)

Publication Title
Oncology Reports
Publication Title Alternative
Oncol Rep.
Volume
34
Issue
6
Start Page
2987
End Page
2996
Publisher
Spandidos Publications
Published Date
2015-09-17
ISSN
1021-335X
NCID
AA11016405
PMID
26398221
DOI
10.3892/or.2015.4284
Resource Type
Thesis or Dissertation
Language
eng
Resource URL
https://doi.org/10.3892/or.2015.4284
Rights
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
Text Version
ETD
Grant ID
博甲第619号
Grant Date
2015-12-25
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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