替莫唑胺诱导的人脑胶质瘤耐药细胞系的建立及其耐药性逆转  

Establishment of Drug-resistance Cell Line of Human Glioma Induced by Temozolomide and Reversion of Drug-resistance

作　　者：李晓兴[1] 王之敏[2] 左剑玲[1] 许期年[1] 王秀云[1] 陶承[1] 

机构地区：[1]苏州大学附属第一医院神经外科,江苏苏州215006 [2]上海交通大学苏州九龙医院神经外科,江苏苏州215123

出　　处：《苏州大学学报（医学版）》2007年第2期169-171,共3页Suzhou University Journal of Medical Science

基　　金：国家自然科学基金资助项目(No.30200335)

摘　　要：目的 建立对替莫唑胺（temozolomide,TMZ）耐药的胶质瘤细胞系并探讨其逆转方式。方法 通过体外分步诱导法使人脑胶质瘤U251细胞对TMZ产生耐药性;利用细胞集落形成实验检测U251/TR的耐药指数;采用MTT法检测O^6-BG对TMZ的细胞毒反转效应。结果 历经6个月建立了对TMZ耐药的U251/TR,在0.25-16μg/mlTMZ培养液中,其细胞形成相对率是未诱导组U251细胞的4-11倍;U251/TR对TMZ的耐药指数约为4;MGMT抑制剂O^6-BG可明显增加TMZ对耐药系的细胞毒作用。结论 通过分步诱导法在体外建立了一株对TMZ耐药的细胞系,其耐药性可被O^6-BG成功地逆转成药敏细胞。Objective To establish a drug-resistance cell line of human glioma with temozolomide （TMZ） and explore how to reverse its drug-resistance. Methods Chemotherapeutic resistance in U251 human glioma cells was caused by the stepwise revulsion with temozolomide（TMZ）. The resistance index and the cell cloning experiment were assayed;MTT was used to assay the effect of O^6-BG to TMZ on cytotoxicity reversal. Results A subline-U251/-FR was developed in 6-month culture; The cell cloning experiment demonstrated that the colony-foming efficency of U251/-FR cells induced stepwisely in TMZ was 4-11 fold that of U251 cells not being induced, in cell culture with 0.25-16 μg/ml TMZ. The depletion of MGMT by O^6-benzylguanine （O^6-BG） significantly increased the cytotoxicity of TMZ in resitant cell lines. Conclusion A drug-resistace cell line of human glioma is devel- oped by the stepwise revulsion with TMZ and the drug-resistance is reversed successfully by O^6-BG.

关 键 词：替莫唑胺 脑胶质瘤 耐药性 

分 类 号：R730.264.05[医药卫生—肿瘤] R979.1[医药卫生—临床医学]