塞来昔布抑制胃癌多药耐药基因表达的研究

Selective cyclooxygenase-2 inhibitor down-regulates the expression of multidrug resistance gene in gastric cancer cells

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 BGC823细胞株经不同浓度的塞来昔布处理后,用ELISA法检测胃癌细胞前列腺素E2(PGE2)的分泌;24,48h后用RT-PCR检测多药耐药MDR1mRNA的表达,48h后用免疫细胞化学染色法检测P-gp的表达。结果塞来昔布可显著抑制胃癌细胞株BGC823的PGE2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MDR/P-gp表达受不同程度抑制,100μmol/L的塞来昔布对MDRlmRNA表达抑制作用强于10μmol/L(P<0.01)。作用48h与24h相比,塞来昔布对MDRlmRNA表达的抑制作用更强(P<0.01)。结论塞来昔布可抑制BGC823MDR1/P-gp的表达,且呈量效关系。其可能通过抑制COX-2活性而抑制PGE2表达,最终抑制P-gp的表达。

Objective To investigate the effect of celecoxib,a selective cyclooxygenase-2 inhibitor,to down-regulate the expression of multidrug resistance （mdrl） gene in the 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 mdrlmRNA were detected by RT-PCR.P-gp protein expression in BGC823 cells was detected by immunocytochemical technique after celecoxib treatment.Results Celecoxib inhibited the expression of PGE2 in a dose dependent manner（P0.05,P0.01）.Same effective situation between the concentration was found on the P-gp expression during the treatment with celecoxib; while the expression of mdrlmRNA was down regulated more effectively after 48 h treatment when compared to that in 24 hs treatment group（P0.01）.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 overcoming the chemotherapeutic resistance of gastric cancer cells.