Significant growth suppression of synovial sarcomas by the histone deacetylase inhibitor FK228 in vitro and in vivo

Tatsuo Ito, Mamoru Ouchida, Yuki Morimoto, Aki Yoshida, Yoshimi Jitsumori, Toshifumi Ozaki, Hiroshi Sonobe, Hajime Inoue, Kenji Shimizu

Research output: Contribution to journalArticle

80 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)311-319
Number of pages9
JournalCancer Letters
Volume224
Issue number2
DOIs
Publication statusPublished - Jun 28 2005

Keywords

  • Growth inhibition
  • Histone deacetylase inhibitor
  • In vivo
  • Synovial sarcoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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