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 & OBJECTIVE:Previous studies using glioma cell lines demonstrated that the expression of ERCC2, a important factor in nucleotide excision repair(NER) system, is associated with chemoresistance of carmustine(BCNU). Whether there is association between the expression of ERCC2 and chemoresistace in human primary glioma samples is unknown. In this article, we investigated the relationship between ERCC2 mRNA expression level and in vitro chemosensitivity in primary human glioma samples. METHODS: Human glioma specimens were obtained during surgery.Chemosensitivity of the tumors to 4 agents, cisplatium(DDP), BCNU, vincristine(VCR) and teniposide(VM26) were determined by the methylthiazole tetrazolium (MTT) assay. ERCC2 expression level in the glioma samples was quantified using real-time quantitative reverse transcription-PCR. RESULTS: Sixty-one fresh glioma specimens from Cancer Center, Sun Yat-sen university were obtained. Result of MTT assay were achieved in 49 cases. The inhibitory rate at PPC(plasma peak concentration) of DDP, BCNU, VCR and VM26 were (37.8±2.6)%,(29.7±3.1)%,(31.3±2.7)%, and (40.7±2.7)%, respectively. ERCC2 mRNA leveles were also varied ranging from 0.01 to 10.50. Spearman analysis showed significant association between ERCC2 expression level and BCNU resistance(P=0.004), but not with DDP,VCR and VM26. CONCLUSION: Our results indicated that ERCC2 mRNA expression is associated with BCNU resistance, but not to DDP, VCR and VM26 resistance in human primary gliomas.