卵巢癌紫杉醇耐药细胞株OC_3/TAX_(300)建立及基因表达谱分析  

Establishment of taxol-resistant ovarian carcinoma cell line OC-3/TAX_(300) and gene expression analysis

作　　者：李红霞[1] 关新元[2] 

机构地区：[1]北京世纪坛医院妇产科,北京100038 [2]香港大学临床肿瘤学系

出　　处：《肿瘤》2006年第8期743-747,共5页Tumor

基　　金：首都医学发展科研基金(重点学科)资助项目(编号:首都ZD199915)

摘　　要：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 paelitaxel （taxol）-resistant human ovarian carcinoma cell line and investigate the relationship between gene differential expression and taxol resistance. Methods： A taxol-resistant human ovarian carcinoma subline OC-3/ TAX300 was established through repeatedly exposing human ovarian cancer OC-3 cells to high concentrations of taxol. Comparative genomie hybridization （CGH） was performed to detect the change in DNA copy number and eDNA micro-array was used to detect gene differential expression. Resuits：OC-3/TAX300 cell line was established after 10 months. It showed stable resistance with drug resistance index （RI） of 6.70. CGH results showed that the chromosome 2p22 of OC3/TAX300 cell was amplified at high level. The eDNA micro-array analysis identified 134 genes differentially expressed in the taxol-resistant cell clone including 117 down-regulated genes and 17 up-regulated genes. The KCNK2 and COP9 genes were down-regulated and JAK2 gene was upregulated. Conclusion：The established OC-3/TAX300 subline has stable resistance to taxol. It is an ideal model for screening drug-resistant genes and drug-resistance reversal agents. The high amplification of chromosome 2p22,down-regulation of KCNK and COP9 genes, and up-regulation of JAK2 gene may be associated with drug-resistance of ovarian cancer to chemotherapy.

关 键 词：卵巢肿瘤 紫杉醇 多药抗药相关蛋白类 细胞 培养的 基因表达调控 基因组印迹 

分 类 号：R737.31[医药卫生—肿瘤]