选择性环氧合酶-2抑制剂塞来昔布抑制胃癌多药耐药基因表达的实验研究

Effect of selective cyclooxygenase-2 inhibitor on expression of multidrug resistance gene in gastric cancer cell

目的:探讨选择性环氧合酶(COX-2)抑制剂塞来昔布对胃癌细胞株BGC823多药耐药(mdr)1表达的影响。方法:胃癌细胞株BGC823经浓度分别为0、10、100μmol/L的塞来昔布处理后,酶联免疫吸附试验检测塞来昔布对胃癌细胞前列腺素E2(PGE2)分泌的影响,24、48h后用RT-PCR检测多药耐药(mdr)1 mRNA表达,48h后用免疫细胞化学染色法检测P-gp表达。结果:塞来昔布可显著抑制胃癌细胞株BGC823PGE2分泌。并呈浓度依赖性(P<0.05)。不同浓度塞来昔布作用于细胞后,胃癌细胞株BGC823的mdrl/P-gp表达受不同程度抑制,100μmol/L的塞来昔布对mdrl mRNA表达抑制作用强于10μmol/L(P<0.01)。不同浓度药物与测量时间为交互作用,作用48h与24h相比,塞来昔布对mdrl mRNA表达的抑制作用更强(P<0.01)。结论:塞来昔布可抑制BGC823的mdr1/P-gp表达,且呈剂量效应关系。塞来昔布可能通过抑制COX-2活性,抑制COX-2下游产物PGE2表达,从而抑制P-gp表达。选择性COX-2抑制剂可能有助于减轻肿瘤细胞对化疗药物的耐药性。

Objective：To investigate the effect of celecoxib,selective cyclooxygenase-2 inhibitor,on the expression of multidrug resistance gene in gastric cancer cell BGC823.Methods：BGC823 cells were treated with celecoxib in different concentrations（0,10μmol/L and 100μmol/L） respectively.Prostaglandin E2（PGE2） was detected by ELISA.Twenty four hs and 48 hs later,the expression of mdrl mRNA were detected by RT-PCR.P-gp protein expression in BGC823 cells was detected by immunocytochemical technique after celecoxib treatment.Results：Celecoxib can inhibit the expression of PGE2 in a dose dependent manner（P〈0.05,P〈0.01）.Same effective situation between the treatment time and the concentration was found on the P-gp expression during the treatment of cele-coxib,while the expression of mdrl mRNA was down regulated more effectively after 48 hs treatment when compared to that in 24 hs treatment group（P〈0.01）.Conclusions：Celecoxib can inhibit the expression of mdrl/P-gp in a time and dose dependent manner.Which is likely to be through inhibiting COX-2 activity.The results suggest that a selective COX-2 inhibitor may play a potential role in over-coming the chemotherapeutics resistance of gastric cancer cells.