5-Aza2-cdR诱导Raji细胞p15基因再表达及细胞生长抑制遗传性的实验研究

目的 :探索 5 - Aza2 - cd R(甲基转移酶抑制剂 )对甲基化细胞系 Raji细胞的生长抑制效应、去甲基化 p1 5基因的再表达 ,及 p1 5基因的再表达遗传性。方法 :对 5 - Aza2 - cd R体外处理高甲基化致 p1 5基因失活的淋巴肉瘤白血病细胞株 Raji细胞 ,细胞生物学特征观察细胞的生长抑制效应。用去甲基化因子 5 - Aza2 - cd R诱导 p1 5基因甲基化的淋巴瘤细胞株Raji细胞 ,RT- PCR方法测定 p1 5基因的表达。结果 :在 1 0 - 7～ 1 0 - 6 M浓度的范围内 ,随着药物浓度的升高 ,Raji细胞生长受到抑制 ,并表现出剂量时间依赖关系 ,细胞生长抑制。在 1 0 - 7和 5× 1 0 - 7M诱导 Raji细胞时 ,p1 5基因去甲基化再表达和生长抑制分别为 6代和 7代。结论 :甲基转移酶抑制剂治疗抗 DNA甲基化的白血病是可行的 ,值得进一步探索。

Transmissibility Of p15 gene expression and inhibitory effect of 5-Aza2-cdR on proliferation of Raji cell lines

Objective:To investigate inhibitory effect on proliferation of Raji cell lines in which p15 gene hymethylate with methylation inhibitor(5-Aza2-deoxytindine), and the transmissibility of inhibitory effect and p15 gene reexpression by demethylation .Methods:Methylation inhibitor, 5-Aza2-deoxytindine was used to treat lymphoma leukemia cell lines Raji ,to investigate inhibitory effect on proliferation by biological characteristics. and RT-PCR was adopted to investigate the p15 gene reexpression of Raji cell lines before and after 5-Aza2-cdR inducing. Results:The results indicated that 5-Aza2-deoxyti ndine showed concentration-dependent and time-dependent inhibition of cell proliferation in 10 -7～10 -6M, and that the transmissibility of inhibitory effect and p15 gene reexpression were seen in sixth generation by 10 -7M compared with seventh generation by 5×10 -7M .Conclusion:It is concluded that it is possible to treat leukemia in which DNA methylate with methyltransferase inhibitors and it is worthwhile to make a thorough study on mechanism of the new strategy.