Effect of the anti-diabetic drug metformin in hepatocellular carcinoma in vitro and in vivo

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/27635
Title
Effect of the anti-diabetic drug metformin in hepatocellular carcinoma in vitro and in vivo
File
Description

Abstract

Metformin is a commonly used oral anti-hyperglycemic agent of the biguanide family. Recent studies suggest that metformin may reduce cancer risk and improve prognosis. However, the antitumor mechanism of metformin in several types of cancers, including hepatocellular carcinoma (HCC), has not been elucidated. The goal of the present study was to evaluate the effects of metformin on HCC cell proliferation in vitro and in vivo, and to study microRNAs (miRNAs) associated with the antitumor effect of metformin in vitro. We used the cell lines Alex, HLE and Huh7, and normal hepatocytes to study the effects of metformin on human HCC cells. In an in vivo study, athymic nude mice bearing xenograft tumors were treated with metformin or left untreated. Tumor growth was recorded after 4 weeks, and the expression of cell cycle-related proteins was determined. Metformin inhibited the proliferation of Alex, HLE and Huh7 cells in vitro and in vivo. Metformin blocked the cell cycle in G0/G1 in vitro and in vivo. This blockade was accompanied by a strong decrease of G1 cyclins, especially cyclin D1, cyclin E and cyclin-dependent kinase 4 (Cdk4). In addition, microRNA (miRNA) expression was markedly altered by the treatment with metformin in vitro and in vivo. In addition, various miRNAs induced by metformin also may contribute to the suppression of tumor growth. Our results demonstrate that metformin inhibits the growth of HCC, possibly by inducing G1 cell cycle arrest through the alteration of microRNAs.

(医博甲596)

Author
著者 三好 久昭
著者(ヨミ) ミヨシ ヒサアキ
著者(別表記) Miyoshi Hisaaki
Publication Title
International Journal of Oncology
Publication Title Alternative
Int J Oncol.
Volume
45
Issue
1
Start Page
322
End Page
332
Publisher
Spandidos Publications
Published Date
2014-05-06
ISSN
1019-6439
NCID
AA10992511
PMID
24806290
DOI
10.3892/ijo.2014.2419
Resource Type
Thesis or Dissertation
Language
eng
Resource URL
https://doi.org/10.3892/ijo.2014.2419
Rights
Copyright © Spandidos Publications 2014
"This is the Publisher's version of the following article: Effect of the anti-diabetic drug metformin in hepatocellular carcinoma in vitro and in vivo; International Journal of Oncology; Volume 45 Issue 1 (2014) Pages: 322-332; doi: 10.3892/ijo.2014.2419, which has been published in final form at https://doi.org/10.3892/ijo.2014.2419 . "
Text Version
ETD
Grant ID
博甲第596号
Grant Date
2014-06-25
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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