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Author
Matsumoto, Yohsuke
Motoki, Takahiro
Takigawa, Masaharu Kaken ID publons researchmap
Tsubouchi, Hirohito
Abstract
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.
Keywords
hepatocyte growth factor
valproic acid
histone deacetylase inhibitor
butyric acid
trichostatin A
induction
tumor invasion
dermal fibroblast
Note
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
Published Date
2008-02-01
Publication Title
Biochemical and Biophysical Research Communications
Volume
volume366
Issue
issue1
Publisher
Academic Press
Start Page
110
End Page
116
ISSN
0006-291X
NCID
AA00564395
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
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