The Effect Of Paclitaxel On The Expression Of Cyclooxygenase-2 And P-glycoprotein In Human Gastric Adenocarcinoma Cell Line BGC-823

Background & Objective: The chemotherapy-induced multi-drug resistance of tumor cells always influences the chemotherapy effect. One of the mechanism is chemotherapy-induced multi-drug resistance (MDR) induced by the increasing expression of P-giycoprotein(P-gp) which is the expression product of MDR-1 .Recent years many researches found that P-gp-mediated cyclooxygenase-2(COX-2) can have some relevance with MDR,and the role of COX-2 in mechanism and function of tumor MDR is being payed more attention to.We take human gastric adenocarcinoma cell line BGC823 as our research object and observe the effect of paclitaxel and a selective COX-2 inhibitor named celecoxib on the expression of COX-2 and P-gp in gastic adenocarcinoma cell line BGC823. To find out the action of COX-2 inhibitor on reverse MDR by compared between paclitaxel-induced apoptosis and the apoptosis after paclitaxel and celecoxib co-treatment, and to study the role that COX-2 played in the mechanism of MDR.Methods: Human gastric adeno-carcinoma cell line BGC-823 were normally cultured and the drug was added 24h after cell line were transferred. The effects of paclitaxel with various doses and time points on BGC823 cell growth was assessed by MTT assay, so did the effects of celecoxib with different doses,and the test doses were determined. We detected the effect of a dose-ranging paclitaxel in at one time point and the change of combining celecoxib with paclitaxel on the COX-2 and P-gp protein expression by western blot.we examined the DNA content of BGC823 cell cycle with PI staining in flow cytometry, to analyze and compare between apoptosis of paclitaxel-induced with a series of concentrations and the apoptosis after different doses paclitaxel and non cyto toxicity dose celecoxib co-treatment.Results: Paclitaxel had the effect of cytotoxicity on BGC823 growth, which in dose-dependent and time-dependent manner.With a limited ranging dose and at a time piont, when the dose of paclitaxel increasing gradually, the expression of both COX-2 and P-gp showed rising trend in BGC823 cell line. And the expression of the two proteins could indicate a downtrend after combined with celecoxib.The BGC823 cell line apoptosis of paclitaxel and non celecoxib co-treatment was markedly enhanced compared with the apoptosis of paclitaxel-induced, celecoxib could improve paclitaxel-induced apoptosis.Conclusions: Paclitaxel can induce the increased expression of COX-2 and P-gp in BGC823 at the same time, and the enhanced expression could be inhibited by celecoxib. Celecoxib could improve paclitaxel-induced apoptosis, and its mechanism is probably associated with the down-regulated COX-2 and P-gp mediated by celecoxib.The inducing of COX-2 expression should take a important part in paclitaxel-induced expression of P-gp.