Frequent methylation of RASSF1A in synovial sarcoma and the anti-tumor effects of 5-aza-2'-deoxycytidine against synovial sarcoma cell lines.
OBJECTIVE
In this study, the methylation status of RASSF1A in synovial sarcomas and the effect of demethylation 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-20-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-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 (P\0.01).


CONCLUSIONS
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.
Numoto
Kunihiko
K
Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558, Japan. numokuni@yahoo.co.jp
Yoshida
Aki
A
Sugihara
Shinsuke
S
Kunisada
Toshiyuki
T
Morimoto
Yuki
Y
Yoneda
Yasushi
Y
Fujita
Yasuko
Y
Nishida
Keiichiro
K
Ouchida
Mamoru
M
Ozaki
Toshifumi
T
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019175:DNA Methylation; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D020128:Inhibitory Concentration 50; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013584:Sarcoma, Synovial / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000964:Antimetabolites, Antineoplastic; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D000077209:Decitabine; D001374:Azacitidine