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ID 32971
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Author
Ito, Tatsuo
Morimoto, Yuki
Yoshida, Aki
Jitsumori, Yoshimi
Sonobe, Hiroshi
Inoue, Hajime
Abstract
About 97% of synovial sarcomas harbor the SYT-SSX fusion gene by chromosomal translocation. We found that the histone deacetylase (HDAC) inhibitor FK228 significantly suppressed the growth of synovial sarcoma cells as compared with that of osteosarcoma. The 50% growth inhibition IC50 value we obtained for FK228 was 0.02-0.2 nM, and it indicates that its suppression effect on synovial sarcoma cells is the highest of any of the HDAC inhibitors yet reported. It was not likely that the growth suppression of FK228 depends on the doubling time of these cells. Introduction of SYT-SSX cDNA into HEK293 cells enhanced the sensitivity of the cells for FK228. Immunostaining of the FK228-treated cells using an anti-acetyl-histone H3 antibody showed that FK228 inhibits deacetylation of histone. In a mice assay, the growth of synovial sarcoma cells was markedly inhibited by FK228 treatment, and the invasion of tumors into surrounding tissues was suppressed. These results suggest that FK228 may be useful in developing therapeutic strategies to treat synovial sarcoma.
Keywords
histone deacetylase inhibitor
synovial sarcoma
growth inhibition
in vivo
Note
Digital Object Identifer:10.1016/j.canlet.2004.10.030
Published with permission from the copyright holder. This is the author's copy, as published in Cancer Letters, June 2005, Volume 224, Issue 2, Pages 311-319.
Publisher URL:http://dx.doi.org/10.1016/j.canlet.2004.10.030
Direct access to Thomson Web of Science record
Copyright © 2004 Elsevier Ireland Ltd. All rights reserved.
Published Date
2005-06-28
Publication Title
Cancer Letters
Volume
volume224
Issue
issue2
Publisher
Elsevier Ireland Ltd.
Start Page
311
End Page
319
ISSN
0304-3835
NCID
AA00598513
Content Type
Journal Article
language
英語
Copyright Holders
Elsevier Ireland Ltd.
File Version
author
Refereed
True
DOI
PubMed ID
Web of Science KeyUT
Submission Path
biology_general/28