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目的：建立人卵巢癌紫杉醇耐药细胞株,探讨其基因表达谱差异与紫杉醇耐药之间相关性。方法：采用反复大剂量紫杉醇冲击法,由亲本细胞OC_3建立卵巢癌紫杉醇耐药细胞株OC_3/TAX_(300)。运用比较基因组杂交(comparative genomic hy- bridization,CGH)及基因芯片技术分析耐药及敏感株细胞染色体DNA拷贝数和基因表达谱差异。结果：OC_3/TAX_(300)耐药株历时10个月建成,耐药性稳定,耐药指数为6.70。CGH结果显示OC_3/TAX_(300)细胞染色体2p22的高水平扩增。基因表达谱芯片共筛选出显著表达差异基因134条,其中117种基因表达水平下调,17种基因表达上调,有代表性的下调基因为KCNK2、COP9,上调的基因为JAK2。结论：建立卵巢癌紫杉醇耐药细胞株OC_3/TAX_(300),耐药性稳定,可以作为筛选耐药基因和耐药逆转剂的细胞模型。OC_3/TAX_(300)细胞染色体2p22的高度扩增、KCNK2、COP9基因下调和JAK2基因上调与卵巢癌化疗耐药有关。
OBJECTIVE: To establish a paclitaxel resistant human ovarian cancer cell line and investigate the relationship between the difference of gene expression profile and paclitaxel resistance. Methods: The paclitaxel - resistant ovarian cancer cell line OC_3 / TAX_ (300) was established from the parental cells OC_3 by repeated high dose paclitaxel impacting. Comparative genomic hybridization (CGH) and cDNA microarray were used to analyze the difference of the copy number and the gene expression profile between chromosomes of resistant and susceptible strains. Results: The OC_3 / TAX_ (300) drug-resistant strains were established in 10 months with stable drug resistance and the drug resistance index was 6.70. CGH results show a high level of amplification of chromosome 2p22 in OC3 / TAX_ (300) cells. A total of 134 differentially expressed genes were screened out by gene expression microarray, of which 117 genes were downregulated and 17 genes were upregulated. Representative down-regulated genes were KCNK2 and COP9, and up-regulated genes were JAK2. Conclusion: To establish a taxol-resistant ovarian cancer cell line OC_3 / TAX_ (300) with stable drug resistance, which can be used as a cell model for screening drug resistance genes and drug-resistant reversal agents. OC3 / TAX3 (300) cell chromosome 2p22 highly amplified, KCNK2, COP9 gene downregulation and JAK2 gene upregulation of ovarian cancer chemotherapy resistance.