摘要
目的探讨替莫唑胺对人神经母细胞瘤SK-N-SH细胞中MGMT基因启动子区甲基化状态的影响,及该影响与细胞对依立替康敏感性的关系。方法体外培养神经母细胞瘤SK-N-SH细胞株作为对照组,采用替莫唑胺处理的细胞株作为实验组,比较两组细胞中MGMT基因启动子区甲基化状态,Real-time PCR检测两组细胞中MGMT基因的表达变化。用MTT法检测两组细胞对依立替康药物的敏感性。结果替莫唑胺处理组细胞MGMT基因的甲基化程度较对照组显著增加。实验组细胞MGMT基因的表达下调,与对照组比较存在显著差异,两者的表达量差异倍数均值为-3.25±0.71。依立替康对实验组细胞的IC50为2.5mg·L-1,对照组的IC50为5.7mg·L-1。结论替莫唑胺能够通过增加SK-N-SH细胞中MGMT编码基因上游启动子区的甲基化程度,从而下调MGMT编码基因的表达量,进而增加SK-N-SH细胞对依立替康的敏感性。
Objective To explore the effect of temozolomide on the methylation state of MGMT promoter in SK-N-SH, and to research the relationship between its influence and the irinotecan sensitivity. Method The SK-N-SH cell line cultured in vitro were served as control, and the SK-N-SH treated by temozolomide were served as experiment group. The methylation state of MGMT was compared between experiment and control group. Real-time PCR was used to detect the expression level of the MGMT. MTT method were applied to evaluate the sensitivity to irinotecan of the two groups. Results Compared with the control group, the methylation state of MGMT were obviously increased in the experiment group. The expression level of MGMT in experiment group also decreased significantly. Differences multiples between the groups is -3.25 ± 0.71. The IC50 of experiment and control groups were 2.5 mg·L-1 and 5.7 mg·L-1 respectively. Conclusion Temozolomide treatment can increase the methylation state of MGMT, which may result in the decrease of MGMT expression level. Then the temozolomide may further increase the SKNSH cell line sensitivity to irinotecan.
出处
《肿瘤药学》
CAS
2011年第2期118-120,132,共4页
Anti-Tumor Pharmacy
