摘 要 目的: 利用cDNA基因芯片筛查与人脑胶质瘤原发性耐药相关的基因，为获取不同个体胶质瘤化疗药物药敏预报基因提供实验依据。方法: 收集符合要求的临床手术切除的人脑胶质瘤组织标本共6例，原代培养肿瘤细胞；由MTT法检测替尼泊苷（teniposide ，VM-26）对胶质瘤细胞生长的抑制率，按VM-26 45 μg/ml（人血药峰浓度）时抑制率>30%为敏感、≤30%为耐药作为标准，将6例组织细胞分为耐药和敏感2组。cDNA芯片检测结合聚类分析方法筛查瘤细胞中与耐药相关的差异表达基因；以半定量RT-PCR法检测瘤细胞中HDAC1基因表达加以验证。 结果: 根据VM-26对细胞抑制率将6例胶质瘤细胞分为3例VM-26敏感和3例耐药。cDNA芯片结合聚类分析共筛选出有表达差异的基因21个,其中表达上调的基因6个、表达下调的基因15个。将表达差异明显的HDAC1经半定量RT-PCR验证，该基因在6例组织中都有表达，趋势与芯片结果一致。结论: 胶质瘤原发性耐药可能与cDNA芯片筛查到的21个基因相关，其确切的耐药机制需要进一步深入研究。

Abstract Objective: To screen for primary drug resistancerelated genes of human malignant glioma using cDNA microarray, so as to provide evidence for drugsensitive predicting gene for chemodrugs for malignant gliomas of different patients. Method: Six fresh glioma specimens were obtained immediately after surgical resection and were primary cultured. MTT method was used to determine the inhibitory effect of Teniposide (VM26) against gliomas. When 4.5 μg/ml（peak blood drug concentration, 1PPC）was used, the inhibitory rate >30% was considered sensitive and the rate ≤30% was considered resistant; and the 6 specimens were divided into 2 group according to the above standard. cDNA microassay combined with clustering analysis was used to screen for resistancerelated genes. Semiquantitative RTPCR was used for verification of HDAC1 gene expression. Results: Three of the 6 glioma specimens belonged to the drug resistance group and the other 3 to the drug sensitive group. cDNA microarray analysis combined with cluster analysis screened out 21 genes, with 6 upregulated and 15 downregulated. High expression of gene HDAC1 was noticed in all the 6 specimens by semiquantitative RTPCR, and the trend was similar to that by microassay. Conclusion: The primary drug resistance of glioma may be associated with the 21 genes screened by cDNA microarray; the detailed mechanisms for drug controlling still need to discussed in the future.

天津市科技发展计划资助项目(No.033182911)