Anti-diabetic drug metformin inhibits cell proliferation and tumor growth in gallbladder cancer via G0/G1 cell cycle arrest

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28992
Title
Anti-diabetic drug metformin inhibits cell proliferation and tumor growth in gallbladder cancer via G0/G1 cell cycle arrest
File
Description

Abstract

Gallbladder cancer is the most common biliary tract cancer with poor prognosis and wide variation in incidence rates worldwide, being very high in some countries in Latin America and Asia. Treatment of type 2 diabetes with metformin causes a reduction in the incidence of cancer. Till date, there are no reports on the anti-tumor effects of metformin in gall bladder cancer. Therefore, this study evaluated the effects of metformin on the proliferation of human gallbladder adenocarcinoma cells in vitro and in vivo, as well as explored the microRNAs associated with the anti-tumor effects of metformin. Metformin inhibited the proliferation in gallbladder adenocarcinoma cell lines NOZ, TGBC14TKB, and TGBC24TKB, and blocked the G0 to G1 transition in the cell cycle. This was accompanied by strong reduction in the expression of G1 cyclins, especially cyclin D1 and its catalytic subunits including cyclin-dependent kinase 4, and in retinoblastoma protein phosphorylation. In addition, metformin reduced the phosphorylation of receptor tyrosine kinases, especially Tie-2, ALK, PYK, EphA4, and EphA10, as well as angiogenesis-related proteins, including RANTES, TGF-β, and TIMP-1. Moreover, metformin also markedly altered microRNA expression profile leading to an anti-tumor effect. Treatment of athymic nude mice bearing xenograft tumors with metformin inhibited tumor growth. These results suggest that metformin may be used clinically for the treatment of gallbladder adenocarcinoma.

(医博甲745)

Author
著者 山下 拓磨
著者(ヨミ) ヤマシタ タクマ
著者(別表記) Yamashita Takuma
Publication Title
Anti-cancer drugs
Publication Title Alternative
Anticancer Drugs.
Volume
31
Issue
3
Start Page
231
End Page
240
Publisher
Lippincott, Williams & Wilkins
Published Date
2020-03
ISSN
0959-4973
NCID
AA12554683
PMID
31815765
DOI
10.1097/CAD.0000000000000870
Resource Type
Thesis or Dissertation
Language
eng
Rights
"This is the Accepted Version of the following article: Anti-diabetic drug metformin inhibits cell proliferation and tumor growth in gallbladder cancer via G0/G1 cell cycle arrest; Anti-cancer drugs; Volume 31 Number 3 (2020) Pages: 231-240; doi: 10.1097/CAD.0000000000000870, which has been published in final form at https://doi.org/10.1097/CAD.0000000000000870 . "
This article is distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/).
Text Version
none
Grant ID
博甲第745号
Grant Date
2020-03-24
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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