Therapeutic potential of the antidiabetic drug metformin in small bowel adenocarcinoma.

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28453
Title
Therapeutic potential of the antidiabetic drug metformin in small bowel adenocarcinoma.
File
Description

Abstract

Small bowel adenocarcinoma (SBAC) accounts for 3% of all gastrointestinal tract tumors and approximately 0.5% of all cancer cases. Recent studies have indicated that the use of metformin, one of the most commonly prescribed antidiabetic drugs, is associated with a better prognosis for certain malignant diseases. However, there have been no reports on the effect of metformin in SBAC. In the present study, we evaluated the effect of metformin on human SBAC cell proliferation in vitro and in vivo and identified the microRNAs (miRNAs) associated with its antitumor effects. Metformin inhibited the proliferation of HuTu80 cells in a time- and dose-dependent manner. Importantly, metformin reduced the expression of cyclin D1, cyclin E, cyclin-dependent kinase 4, and phosphorylated retinoblastoma protein, which resulted in cell cycle arrest at the G0/G1 phase. This arrest was accompanied by activation of AMPKα and inhibition of mammalian target of rapamycin and p70s6k. Additionally, metformin reduced the levels of phosphorylated epidermal growth factor receptor and ROR2 as well as markedly altered miRNA expression in HuTu80 cells. Metformin also inhibited tumor growth in vivo in a xenograft mouse model. Our data suggest that metformin might have therapeutic potential in SBAC.

(医博甲682)

Author
著者 千代 大翔
著者(ヨミ) チヨ タイガ
著者(別表記) Chiyo Taiga
Publication Title
International Journal of Oncology
Publication Title Alternative
Int J Oncol.
Volume
50
Issue
6
Start Page
2145
End Page
2153
Publisher
Spandidos Publications
Published Date
2017-04-20
ISSN
1019-6439
NCID
AA10992511
PMID
28440424
DOI
10.3892/ijo.2017.3971
Resource Type
Thesis or Dissertation
Language
eng
Relation
出版社版DOIリンク(URL): https://doi.org/10.3892/ijo.2017.3971
Resource URL
https://doi.org/10.3892/ijo.2017.3971
Rights
Copyright © Spandidos Publications 2017.
"This is the Publisher's version of the following article: Therapeutic potential of the antidiabetic drug metformin in small bowel adenocarcinoma.; International Journal of Oncology; Volume 50 Issue 6 (2017) 2145-2153; doi: 10.3892/ijo.2017.3971, which has been published in final form at https://doi.org/10.3892/ijo.2017.3971 ."
Publisher's Version (DOI): https://doi.org/10.3892/ijo.2017.3971
Text Version
ETD
Grant ID
博甲第682号
Grant Date
2018-03-24
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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