氨甲蝶呤获得性耐药和DNA甲基化的相关性研究  

The study on the relationship between acquired drug resistance to methotrexate and global DNA methylation

作　　者：李明[1,2] 沈佐君[1] 何晓东[1] 陶绍能[1] 董林[1] 朱园园[1] 吴剑锋[1] 

机构地区：[1]安徽医科大学附属省立医院省临检中心,合肥230001 [2]合肥市疾病预防控制中心,合肥230082

出　　处：《安徽医科大学学报》2009年第5期570-573,共4页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金项目(编号:30672011);安徽省自然科学基金资助项目(编号:050430902);安徽省人才开发资金资助项目(编号:2005Z040)

摘　　要：目的研究氨甲蝶呤(MTX)获得性耐药与DNA甲基化的相关性。方法采用浓度递增结合低剂量持续诱导的方法诱导细胞发生MTX耐药。通过高效毛细管法检测非小细胞肺癌A549细胞和非小细胞肺癌A549/MTX细胞内整体DNA甲基化水平。结果MTT法分析显示A549细胞对MTX发生耐药。A549细胞发生MTX耐药时,其甲基化水平明显降低,且随着MTX耐药浓度增加,耐药细胞株DNA甲基化程度依次降低。A549/MTX细胞和A549细胞整体DNA甲基化水平差异有统计学意义。结论MTX获得性耐药引起细胞内整体DNA甲基化水平降低,MTX获得性耐药机制可能与DNA甲基化相关。Objective To study the relationship between acquired drug resistance to methotrexate and global DNA methylation. Methods Nonsmall cell lung cancer A549 which cells were rendered acquired drug resistance to methotrexate by treatment with the increasing of methotrexate dose. Global DNA methylation levels in A549 and A549/MTX cells were detected using high performance capillary electrophoresis. Results A549/MTX cells were resistant to methotrexate as evaluated by MTT assay. Percentage of mdC decreased with the increasing of drug-resistance concentrations in A549/MTX ceils. Conclusion The data sugguests that acquired drug resistance to methotrexate make global DNA hypermethylation in cellular, and the mechanisms of acquired drug resistance to methotrexate may be concerned with DNA methylation.

关 键 词：氨甲蝶呤 DNA甲基化 电泳 毛细管 

分 类 号：R394[医药卫生—医学遗传学] R979.12[医药卫生—基础医学]