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背景与目的:以往细胞株的研究提示,核苷酸切除修复系统中的重要因子ERCC2表达与BCNU耐药相关,然而在人脑胶质瘤是否同样如此,还没有明确资料。本研究将对人脑胶质瘤临床标本进行体外药敏试验,并分析其与ERCC2表达的关系。方法:在人脑胶质瘤手术时收集新诊断的原发性胶质瘤新鲜标本61例,采用MTT法进行体外药敏试验,测定脑瘤常用化疗药DDP、BCNU、VCR和VM26的敏感性。并对收集的肿瘤标本采用实时定量RT-PCR方法检测ERCC2mRNA的表达,然后对二者结果进行相关性分析。结果:体外药物敏感性检测中,49例样本获得成功检测,成功率达到80%。体外药敏结果在49例样本中差别较大。四种化疗药物DDP、BCNU、VCR和VM26在血浆峰浓度下的肿瘤生长抑制率(IR)分别为(37.8±2.6)%、(29.7±3.1)%、(31.3±2.7)%和(40.7±2.7)%。49例肿瘤标本的ERCC2mRNA相对表达范围较广,为0.01￣10.50。相关性分析显示ERCC2表达同BCNU敏感性负相关(Spearman相关系数为-0.373,P=0.004),而与DDP、VCR以及VM26的敏感性没有统计学意义。结论:人脑胶质瘤组织中ERCC2mRNA表达与BCNU敏感性相关,但与DDP、VCR和VM26的体外敏感性无关。
BACKGROUND AND AIM: Previous studies of cell lines suggested that ERCC2, an important factor in the nucleotide excision and repair system, is associated with resistance to BCNU. However, no clear data are available in human gliomas. In this study, human glioma clinical specimens in vitro susceptibility testing and analysis of ERCC2 expression. Methods: Sixty-one newly diagnosed primary glioma samples were collected during human glioma surgery. MTT assay was used to determine the sensitivity of commonly used chemotherapy drugs DDP, BCNU, VCR and VM26 in brain tumors . The expression of ERCC2 mRNA in the collected tumor samples was detected by real-time quantitative RT-PCR, and the correlation between the two results was analyzed. Results: In vitro drug sensitivity test, 49 cases of successful detection, the success rate reached 80%. In vitro susceptibility results in 49 cases of large differences. The tumor growth inhibitory rates (IR) of the four chemotherapeutic drugs DDP, BCNU, VCR and VM26 at peak plasma concentrations were (37.8 ± 2.6)%, (29.7 ± 3.1)%, (31.3 ± 2.7)% and 2.7)%. 49 cases of tumor specimens ERCC2mRNA relative expression of a wide range of 0.01 ~ 10.50. Correlation analysis showed that the expression of ERCC2 was negatively correlated with BCNU sensitivity (Spearman correlation coefficient -0.373, P = 0.004), but not with DDP, VCR and VM26. Conclusion: The expression of ERCC2 mRNA in human glioma tissue is related to the sensitivity of BCNU, but not to the sensitivity of DDP, VCR and VM26 in vitro.