临床肿瘤学杂志

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COX-2通过NF-κB通路上调胃癌细胞P-gp表达的实验研究

陈玉,顾康生   

  1. 230022 合肥 安徽医科大学第一附属医院肿瘤内科
  • 收稿日期:2012-01-03 修回日期:2012-03-06 出版日期:2012-07-31 发布日期:2012-07-31
  • 通讯作者: 顾康生

Experimental study of cyclooxygenase-2 up-regulates P-glycoprotein expression through NF-κB pathway on human gastric adenocarcinoma cell line SGC-7901

CHEN Yu,GU Kang-sheng   

  1. Department of Oncology,the First Affiliated Hospital of Anhui Medical University,Hefei 230022,China
  • Received:2012-01-03 Revised:2012-03-06 Online:2012-07-31 Published:2012-07-31

摘要: 目的 探讨紫杉醇(TAX)作用下环氧化酶-2(COX-2)诱导胃癌细胞株SGC-7901多药耐药P蛋白(P-gp)表达可能的信号通路。方法 MTT法检测TAX、COX-2抑制剂NS-398和核因子-κB (NF-κB)信号通路抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)不同剂量对胃腺癌细胞株SGC-7901生长的影响;Western blotting检测TAX作用于SGC-7901细胞株以及联合NS-398、PDTC对COX-2、NF-κB p65和P-gp表达的影响。结果 TAX、NS-398和PDTC均对胃癌细胞株SGC-7901的生长具有细胞毒作用,并呈剂量依赖性。TAX(0.1、0.3、0.5μmol/L)可诱导COX-2、p65和P-gp表达,随剂量增加,3种蛋白表达显著增加;与NS-398(5、10μmol/L)联用时,随剂量增加和时间延长,3种蛋白表达减少;与PDTC(0.2μmol/L)联用时,随作用时间延长,p65和P-gp表达减少。结论 在TAX作用下,COX-2可能通过激活NF-κB通路而引起胃癌SGC-7901细胞株P-gp表达增加。

Abstract: Objective To investigate the possible signal pathway of multi-drug resistant P-glycoprotein(P-gp)expression induced by cyclooxygenase-2(COX-2)in hunman gastric adenocarcinoma cell line SGC-7901 stimulating with pacliaxel(TAX). Methods The effects of TAX on SGC-7901 cells growth was assessed by MTT assay,and so did the effects of COX-2 selective inhibitor NS-398 and nuclear factor-κB (NF-κB) pathway inhibitor pyrrolidine dithiocarbamate(PDTC).The effect of a dose-ranging TAX and the change of combining NS-398 or PDTC with TAX on the COX-2,p65 and P-gp expression were detected by Western blotting. Results TAX,NS-398 and PDTC all had the effect of cellular toxicity on SGC-7901 cell line growth in a dose-dependent manner. When the dose of TAX(0.1,0.3,0.5μmol/L) increased,the expression of COX-2,p65 and P-gp showed rising trend in SGC-7901 cell line. And the expression of three proteins could decrease with the increase of dose and extension of time after combined with NS-398(5,10μmol/L). When combined with PDTC(0.2μmol/L),the expression of p65 and P-gp decreased significantly. Conclusion COX-2 may induce the expression of P-gp in SGC-7901 cell line via NF-κB pathway with the stimulation of TAX.

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