NDGA诱导人胶质瘤细胞株分化过程中基因组甲基化及甲基转移酶的变化及意义

目的 了解去甲二氢愈创木酸(Nordihydroguaiaretic acid,NDGA)处理前后两种人胶质瘤细胞系CHC-5、SHC-44甲基转移酶(DNA methyltransferase，DNMT)活性、DBNT mRNA表达和基因组甲基化程度的改变。方法 以NDAG处理人恶性胶质瘤细胞系CHC-5及SHC-44，观察两种细胞增殖和分化状态；采用同位素微量示踪法测定甲基转移酶活性和基因组DNA甲基化程度；应用RT-PCR法测定洲DNMT mRNA表达水平。结果 NDMT处理后两种细胞增殖速度明显减缓，分化水平升高；DNMT活性显著降低、基因组甲基化程度明显升高；而DNMT mRNA改变不明显。结论 NDGA能抑制甲基转移酶的活性，升高基因组甲基化水平，这些作用可能与其诱导恶性胶质细胞瘤分化的机制有关。

Changes of DNA methylation during differentiation of human glioma cells induced by NDGA

Objective To investigate the role of NDGA in changing the activity, expression of the DNA methyltransferase (DNMT) and the patterns of genome DNA methylation in two glioma lines. Methods After two malignant glioma lines CHG 5 and SHG 44 were treated by various concentrations of NDGA, their differentiation states, the patterns of genome methylation, activity of NDMT were detected by 3H labeled tracing microassay technique and RT PCR was used to measure the expression of NDMT mRNA. Results NDGA could reduce the activity of DNMT and increase the DNA methylation degree which was dose and time dependent, but could not change the expression of DNMT mRNA. Conclusion The effect of NDGA on the inhibition of DNMT activity, increase of the DNA methylation degree may be one of the most important mechanisms of NDGA inducing differentiation effect.