Metformin Inhibits Proliferation and Tumor Growth of QGP-1 Pancreatic Neuroendocrine Tumor Cells by Inducing Cell Cycle Arrest and Apoptosis

( 最大 2000 件 )
URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28990
タイトル
Metformin Inhibits Proliferation and Tumor Growth of QGP-1 Pancreatic Neuroendocrine Tumor Cells by Inducing Cell Cycle Arrest and Apoptosis
ファイル
内容記述

Abstract

Background/aim: Pancreatic neuroendocrine tumors (pNETs) are rare pancreatic neoplasms, and therapeutic options for pNETs are limited. Metformin is an anti-hypoglycemic drug that appears to have anticancer effects. However, little is known about the effect of metformin on pNETs. In this study, we investigated the anti-proliferative effect of metformin on a human pNET cell line.

Materials and methods: The anti-proliferative properties of metformin were evaluated in QGP-1 and NCI-H727 cells using a cell counting kit-8 assay. Xenograft mouse models were used to assess the tumor effect in vivo.

Results: Metformin inhibited the proliferation and anti-tumor growth of QGP-1 cells, accompanied by their arrest during the cell cycle at the G0/G1 phase. Immunohistochemical analysis of tumor tissues revealed down-regulation of cyclin D1 and proliferating cell nuclear antigen in the metformin-treated group. Additionally, metformin induced apoptosis, and the expression of survivin and claspin were decreased in metformin-treated QGP-1 cells according to the apoptosis array. Furthermore, the angiogenic related protein TIMP-1 was down-regulated, and its miRNA expression was altered by metformin in QGP-1 cells.

Conclusion: Taken together, our study demonstrated the therapeutic potential of metformin and provides molecular mechanistic insights into its anti-tumoral effect on pNETs. This study is the first one describing anti-tumoral effects in pNETs.

Keywords:

Pancreatic neuroendocrine tumor; apoptosis; cell cycle; metformin; microRNA

(医博甲743)

著者
著者 山名 浩喜
著者(ヨミ) ヤマナ ヒロキ
著者(別表記) Yamana Hiroki
掲載誌
Anticancer research
掲載誌(別表記)
Anticancer Res.
40
1
開始ページ
121
終了ページ
132
出版者
International Institute of Anticancer Research
出版年月日
2020-01
ISSN
0250-7005
NCID
AA12440673
PMID
31892560
DOI
10.21873/anticanres.13933
資料タイプ
学位論文
言語
英語
権利関係
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios).
"This is the Publisher's Version of the following article: Metformin Inhibits Proliferation and Tumor Growth of QGP-1 Pancreatic Neuroendocrine Tumor Cells by Inducing Cell Cycle Arrest and Apoptosis; Anticancer research; Volume 40 Number 1 (2020) Pages: 121-132; doi: 10.21873/anticanres.13933, which has been published in final form at https://doi.org/10.21873/anticanres.13933 . "
Non-commercial use.
エンバーゴ期間満了。 / The embargo period has expired.
博士論文(全文を含む)
学位授与番号
博甲第743号
学位授与年月日
2020-03-24
学位名
博士(医学)
学位授与機関
香川大学
区分
香川大学
Copyright (C) 2009 Kagawa University All rights reserved.