Frequent methylation of RASSF1A in synovial sarcoma and the anti-tumor effects of 5-aza-2′-deoxycytidine against synovial sarcoma cell lines
Frequent methylation of RASSF1A in synovial sarcoma and the anti-tumor effects of 5-aza-2′-deoxycytidine against synovial sarcoma cell lines
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滑膜肉瘤中RASSF1A的频繁甲基化及5-aza-2-脱氧胞苷对滑膜肉瘤细胞系的抗肿瘤作用
DOI：
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发表时间：
2009
影响因子：
3.6
通讯作者：
T. Ozaki
中科院分区：
文献类型：
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作者：
K. Numoto;Aki Yoshida;S. Sugihara;T. Kunisada;Y. Morimoto;Y. Yoneda;Y. Fujita;K. Nishida;M. Ouchida;T. Ozaki
目的检测RASSF1A基因在滑膜肉瘤组织中的甲基化状态及去甲基化对滑膜肉瘤的影响。方法采用甲基化特异性聚合酶链式反应技术检测74例软组织肉瘤(包括21例滑膜肉瘤)中RASSF1A基因的甲基化状态。用滑膜肉瘤细胞系SYO-1和HS-SY-II检测去甲基化药物5-氮-2‘-脱氧胞苷(5-aza-DC)对滑膜肉瘤的作用。结果21例滑膜肉瘤中有10例(47.6%)发生RASSF1A甲基化，53例其他滑膜肉瘤中有10例(18.9%)发生RASSF1A甲基化(P=0.0295)。经5-氮杂胞苷去甲基化处理后，RASSF1a基因重新表达，细胞生长受到抑制。5-氮杂-DC对SYO-1和HS-SY-II细胞的IC_(50)分别为0.9%和1.3gμM(96h)。每周给药1或10 mg/kg的5-aza-DC可显著抑制小鼠SYO-1移植瘤的生长(P<0.01)。结论首次报道了5-aza-DC对滑膜肉瘤的抗肿瘤作用。提示5-氮杂-DC对滑膜肉瘤有良好的治疗潜力。
PurposeIn this study, the methylation status of RASSF1A in synovial sarcomas and the effect of de-methylation on synovial sarcoma were examined.MethodsThe 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).ResultsRASSF1A 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).ConclusionThis 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.
影响因子：
10.3
作者：
Burbee, DG;Forgacs, E;Minna, JD
通讯作者：
Minna, JD
影响因子：
45.3
作者：
Lewis, JJ;Antonescu, CR;Brennan, MF
通讯作者：
Brennan, MF
影响因子：
20.3
作者：
Kantarjian, Hagop;Oki, Yasuhiro;Issa, Jean-Pierre J.
通讯作者：
Issa, Jean-Pierre J.