COX-2转录抑制作用逆转卵巢癌细胞紫杉醇耐药的研究  

Reversal of Paclitaxel-resistance by Suppression of COX-2 Transcriptional Activity in Human Ovarian Cancinoma Cells

作　　者：马雪莲[1] 黄建鸣[2] 张国楠[2] 查晓[2] 任源[2] 吴俊辉[2] 邓碧芳[2] 程佳[2] 

机构地区：[1]广西医科大学,南宁530021 [2]四川省肿瘤医院研究所,成都610041

出　　处：《肿瘤预防与治疗》2010年第2期113-118,共6页Journal of Cancer Control And Treatment

基　　金：四川省科技厅应用基础项目(2006J13-132);成都市科技攻关项目(06GGYB408SF-30)

摘　　要：目的:探讨COX-2转录抑制对卵巢癌细胞MDR1/P-gP表达及紫杉醇敏感性的影响。方法:用逆转录多聚酶链式反应(RT-PCR)检测抑制COX-2促进子活性对人卵巢癌紫杉醇耐药细胞株A2780/PTX的COX-2和MDR1 mRNA表达水平;用免疫细胞化学方法检测A2780/PTX细胞P-gP的表达;用MTT法测定紫杉醇作用A2780/PTX细胞的生长抑制作用。结果:抑制COX-2促进子明显下调A2780/PTX细胞的COX-2和MDR1 mRNA的表达(P<0.05)及其P-gP蛋白表达,以及显著增加了紫杉醇对A2780/PTX细胞的生长抑制作用。Pearson分析显示,MDR1 mRNA与COX-2 mRNA的表达存在明显的依赖关系(R=0.748,P<0.01);结论:A2780/PTX细胞存在COX-2依赖的MDR1/P-gP共表达现象;抑制或沉默COX-2转录可显著逆转COX-2介导的MDR1/P-gP依赖的MDR和增加紫杉醇的敏感性。Objective： To investigate the reversal of paclitaxel-resistance by suppression of COX-2 transcriptional activity in human ovarian cancinoma cells. Methods： Expression of COX-2 and MDR1 mRNA were determined using reverse transcription polymerase chain reaction （ RT-PCR）, and expression of P-glycoprotein （P-gp） was detected by immuocytochemistry in A2780/PTX cells. Growth inhibition of paclitaxel to A2780/PTX cells was determined using MTT assay. Results ： The expression of COX- 2 , MDR1 mRNA and P-gp were downregulated significantly by suppression of COX-2 transcriptional activity for 48hrs （P 〈 0.05 ） in A2780/PTX cells, and the co-expression of MDR1 and COX2 mRNAs in A2780/PTX cells was demonstrated using Pearson＇ s correlation analysis （R = 0.748, P 〈 0.01 ） ; Suppression of COX-2 transcriptional activity increased the inhibitory effects of paclitaxel on the growth of A2780/PTX cells and sensitized A2780/PTX cells to paclitaxel significantly. Conclusion： Our research showed that COX-2 gene might be a target gene for COX-2-dependent MDR1/P-gp expression in A2780/PTX ceils , and suppression of COX-2 expression at the transcriptional level might be involved in regulating COX-2-dependent MDR1/P-gp overexpression, and in reversing paclitaxel-resistance in ovarian cancinoma.

关 键 词：卵巢癌 COX-2 MDR1 P-GP A2780/PTX细胞 A2780细胞 紫杉醇 

分 类 号：R737.31[医药卫生—肿瘤]