Frequent methylation of RASSF1A in synovial sarcoma and the anti-tumor effects of 5-aza-2′-deoxycytidine against synovial sarcoma cell lines

Kunihiko Numoto, Aki Yoshida, Shinsuke Sugihara, Toshiyuki Kunisada, Yuki Morimoto, Yasushi Yoneda, Yasuko Fujita, Keiichiro Nishida, Mamoru Ouchida, Toshifumi Ozaki

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Purpose: In this study, the methylation status of RASSF1A in synovial sarcomas and the effect of de-methylation on synovial sarcoma were examined. Methods: The methylation status in 74 soft tissue sarcomas (STSs) including 21 synovial sarcomas was determined by methylation specific PCR. The effect of the de-methylating agent 5-aza-2′-deoxycytidine (5-Aza-dC) on synovial sarcoma was examined using synovial sarcoma cell lines (SYO-1 and HS-SY-II). Results: RASSF1A methylation was observed in 10 (47.6%) of 21 synovial sarcomas and in 10 (18.9%) of 53 the other STSs (P = 0.0295). De-methylation of the cells by treatment with 5-Aza-dC induced re-expression of RASSF1A and growth suppression of the cells. The calculated IC50 of 5-Aza-dC against the SYO-1 and the HS-SY-II cells were 0.9 and 1.3 μM (96 h), respectively. With twice weekly administration of 1 or 10 mg/kg 5-Aza-dC, the growth of the mouse xenograft tumors of SYO-1 was significantly suppressed in comparison to the controls (P < 0.01). Conclusion: This is the first report showing the anti-tumor effect of 5-Aza-dC on synovial sarcoma. 5-Aza-dC is suggested to have a good therapeutic potential against synovial sarcoma.

Original languageEnglish
Pages (from-to)17-25
Number of pages9
JournalJournal of cancer research and clinical oncology
Volume136
Issue number1
DOIs
Publication statusPublished - Jan 1 2010

Keywords

  • 5-aza-2′-deoxycytidine
  • DNA methylation
  • RASSF1A
  • Soft tissue sarcoma
  • Synovial sarcoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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