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-KB ( NF-kB ) 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, l0μMol/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-kB pathway with the stimulation of TAX.%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-KB通路而引起胃癌SGC-7901细胞株P-gp表达增加.
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