Section 54
Chapter 53,305

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

Numoto, K.; Yoshida, A.; Sugihara, S.; Kunisada, T.; Morimoto, Y.; Yoneda, Y.; Fujita, Y.; Nishida, K.; Ouchida, M.; Ozaki, T.

Journal of Cancer Research and Clinical Oncology 136(1): 17-25


ISSN/ISBN: 1432-1335
PMID: 19578875
DOI: 10.1007/s00432-009-0632-2
Accession: 053304965

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In this study, the methylation status of RASSF1A in synovial sarcomas and the effect of demethylation on synovial sarcoma were examined. 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-20-deoxycytidine (5-Aza-dC) on synovial sarcoma was examined using synovial sarcoma cell lines (SYO-1 and HS-SY-II). 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-SYII cells were 0.9 and 1.3 lM (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 (P0.01). 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.

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