MGMT介导的人脑胶质瘤耐药细胞系的建立

目的：建立由O^6-甲基鸟嘌呤－DNA甲基转移酶（MGMT）介导的人脑胶质瘤耐药细胞株U251／BCNU。方法：模拟卡氮芥（BCNU）的临床用药程序,采取恒定药物浓度、周期性使用的方式诱导U251的抗药性。检测U251／BCNU的耐药指数及MGMT mRNA的表达;比较U251及U251／BCNU细胞的体外增殖变化。结果：经过反复总共5次的用药过程,历时4个月,成功地建立了对BCNU具有稳定抗药性的U251／BCNU,其对BCNU的耐受程度约为U251的17倍。RT－PCR显示,U251／BCNU细胞有MGMTmRNA的表达。U251及U251／BCNU细胞的体外群体倍增时间差异无显著性。结论：在体外成功地建立了一株由MGMT介导的人脑胶质瘤耐药细胞系,为进一步探讨胶质瘤的耐药机制及逆转方式奠定了基础。

Establishment of drug-resistance cell line of human glioma mediated by MGMT

Institute of Neurosurgery,CAMS and PUMC,Beijing100050 Objective To establish a drug-resistance cell line of human glioma mediated by MGMT.Methods Simulated the clinical usage of BCNU to establish a BCNU-resi stant human glioma subline by cyclic exposing the U251parent cells to a co nstant concentration of BCNU.The resistance index and the expression of MGMT mRNA of U251/BCNU were detected and compared the difference of in vitro proli feration between U251and U251/BCNU.Results A subline -U251/BCNU was s uccessfully established in about 4-month culture,which had a stable resistance to BCNU.U251/BCNU cells showed17-fold higher resistance to BCNU than did U251cells by MTT assay,while U251/BCNU cells expressed MGMT mRNA.The d o ubling time of U251and U251/BCNU had no statistical difference.Conclusio n A drug-resistance cell line of human glioma mediated by MGMT is established ,which could provide experimental basis for further studies on the resistance m echanism and reversal methods of glioma chemotherapy.