摘要
背景与目的:胶质瘤的放射治疗效果与其放射敏感性密切相关,有许多因素影响着胶质瘤的放射敏感性。研究已经发现某些基因启动子区CpG岛的甲基化会导致基因的表达沉默,从而影响肿瘤放射敏感性。本文初步探讨了DNA修复基因ERCC1启动子区CpG甲基化与脑胶质瘤放射敏感性的关系。方法:培养4种胶质瘤细胞株MGR1、MGR2、SF767、T98G,集落形成实验法检测其放射敏感性,以2Gy照射后细胞存活集落数(SF2)作为标准表示。应用亚硫酸氢钠修饰后测序的方法对4株细胞中ERCC1基因启动子区CpG岛的甲基化状态进行分析。进而分析其甲基化状态与放射敏感性的关系。结果:4种胶质瘤细胞株的放射敏感性存在较大差异,SF2均数范围从0.18到0.70;在ERCC1启动子区CpG为去甲基化状态细胞株的SF2值较高(MGR1,0.59±0.09;T98G,0.70±0.05),表示对放射线较抗拒;ERCC1启动子区CpG为甲基化状态细胞株的SF2值较低(MGR2,0.18±0.05;SF767,0.32±0.08),表示对放射线较敏感(t=-4.43,P<0.05)。结论:ERCC1启动子区CpG甲基化状态可能与胶质瘤细胞株放射敏感性相关,有希望成为预测胶质瘤放疗敏感性的新指标。
BACKGROUND ＆ OBJECTIVE：Radio-sensitivity of gliomas determines radiotherapy efficacy. Evidence demonstrates that methylation of CpG island in the promoter region results in gene silencing. This study was designed to determine the relationship between methylation status of ERCC1 promoter region and radio-sensitivity in glioma cell lines. METHODS： Surviving fraction at 2GY （SF2） was measured in 4 human glioma cell lines, MGR1, MGR2, SF767 and T98G. by using colony forming experiments. Methylation status in the promoter region of ERCC1 in these glioma cell lines was determined by using bisulphite sequencing. RESULTS： ERCC1 gene promoter CpG islands were methylated in MGR1 and T98G cells, with a SF2 of 0.59±0.09 and 0.70±0.05 respectively. No methylation of ERCC1 gene promoter CpG islands were found in MGR2 and SF767. SF2 of MGR2 and SF767 was 0.18±0.05 and 0.32±0.08 respectively. There was a statistical difference in the radio-sensitivity between glioma cells with and without methylation of ERCC1 gene promoter CpG islands. （t=-4.43,P〈0.05）. CONCLUSION： Our data indicate that methylation status of ERCC1 is associated with radio-sensitivity in gliomas cell lines. It could be used as a new biomarker for predicting the radio-sensitivity of human gliomas.
出处
《中国神经肿瘤杂志》
2007年第3期156-159,共4页
Chinese Journal of Neuro-Oncology
基金
华南肿瘤学国家重点实验室985-Ⅱ基金
