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ID 34245
フルテキストURL
Thumnail fig.pdf 144 KB
Thumnail table.pdf 26.3 KB
著者
Matsumoto, Yohsuke Department of Immunochemistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Motoki, Takahiro Department of Immunochemistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kubota, Satoshi Department of Biochemistry and Molecular Dentistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Takigawa, Masaharu Department of Biochemistry and Molecular Dentistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Tsubouchi, Hirohito Digestive Disease and Life-style Related Disease, Health Research Human and Environmental Sciences, Kagoshima University, Graduate School of Medicine and Dental Sciences
Gohda, Eiichi Department of Immunochemistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
抄録
Hepatocyte growth factor (HGF), which is produced by surrounding stromal cells, including fibroblasts and endothelial cells, has been shown to be a significant factor responsible for cancer cell invasion mediated by tumor-stromal interactions. We found in this study that the anti-tumor agent valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, strongly inhibited tumor-stromal interaction. VPA inhibited HGF production in fibroblasts induced by epidermal growth factor (EGF), platelet-derived growth factor, basic fibroblast growth factor, phorbol 12-myristate 13-acetate (PMA) and prostaglandin E-2 without any appreciable cytotoxic effect. Other HDAC inhibitors, including butyric acid and trichostatin A (TSA), showed similar inhibitory effects on HGF production stimulated by various inducers. Up-regulations of HGF gene expression induced by PMA and EGF were also suppressed by VPA and TSA. Furthermore, VPA significantly inhibited HGF-induced invasion of HepG2 hepatocellular carcinoma cells. VPA, however, did not affect the increases in phosphorylation of MAPK and Akt in HGF-treated HepG2 cells. These results demonstrated that VPA inhibited two critical processes of tumor-stromal interaction, induction of fibroblastic HGF production and HGF-induced invasion of HepG2 cells, and suggest that those activities serve for other anti-tumor mechanisms of VPA besides causing proliferation arrest, differentiation, and/or apoptosis of tumor cells.
キーワード
hepatocyte growth factor
valproic acid
histone deacetylase inhibitor
butyric acid
trichostatin A
induction
tumor invasion
dermal fibroblast
備考
Published with permission from the copyright holder.
This is a author's copy,as published in Biochemical and Biophysical Research Communications, 2008 Vol.366 Issue.1 pp.110-116
Publisher URL: http://dx.doi.org/10.1016/j.bbrc.2007.11.089
Direct access to Thomson Web of Science record
Copyright © 2007 by Elsevier Inc.
発行日
2008-02-01
出版物タイトル
Biochemical and Biophysical Research Communications
366巻
1号
出版者
Academic Press Inc Elsevier Science
開始ページ
110
終了ページ
116
ISSN
0006-291X
NCID
AA00564395
資料タイプ
学術雑誌論文
言語
English
OAI-PMH Set
岡山大学
著作権者
Elsevier Inc.
論文のバージョン
author
査読
有り
DOI
PubMed ID
Web of Sience KeyUT
Submission Path
biochemistry/10