The Effect Of Paclitaxel On Human Gastric Cancer Cell Lines Expressed COX-2 And Possible Signal Transduction Pathway Research

Background & Objective: COX-2 is the rate-limiting enzyme prostaglandin synthesis. Studies have shown that COX-2 expression are closely related to tumor occurrence, development and metastasis, Also affect the efficacy of chemotherapy, which may be related to tumor cells expression of COX-2 by chemotherapeutic drug induced and multidrug resistance occurrence. In vitro, the experiments have showed that chemotheraputic drug taxol can induce gastric cancer cell lines the expression of COX-2 protein and MDR protein at the same time. The expression of COX-2 can induce the expression of MDR protein, and the inhibiting COX-2 expression could reverse MDR expression. Thus, the understanding of signal pathway by paclitaxel -induced gastric cancer cell line COX-2 protein expression is of great significance for exploring the mechanism and reversing resistance in the future. In this experiment, the paclitaxel and P38 pathway signal inhibitor SB203580 were added to culturing human gastric cancer cell line SGC-7901, by comparing to the changes on COX-2 mRNA expression of SGC-7901 after paclitaxel alone and combating paclitaxel with SB203580, we can understand the role of P38 signaling pathway in the paclitaxel -induced SGC-7901 COX-2 expression.Methods: The experiment was initiated after human gastric adenocarcinoma cell lines SGC-7901 subcultured 24h. The effects of paclitaxel on SGC-7901 growth with different doses and time points was assessed by MTT assay, and so did the effects of P38 pathway inhibitor SB203580 with different doses, and the test doses were determined. RT-PCR method was used to detect COX-2 mRNA expression level of SGC-7901 cell line treated by Paclitaxel for 24 hours within a certain concentration range, or in combination with SB203580. we examined the DNA content of SGC-7901 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 noncytotoxicity dose SB203580 co-treatment.Results: Paclitaxel had the effect of cytotoxicity on SGC-7901 growth, which in dose-dependent and time-dependent manners. Within a certain dose range and time poi -nt, COX-2 mRNA expression level was increased as the dose of paclitaxel increasing, and the tendency could be reversed when SB203580 dose increased. The SGC-7901 cell line apoptosis of paclitaxel and non SB203580 co-treatment was markedly enhanced compared with the apoptosis of paclitaxel-induced, SB203580could improve paclitaxel -induced apoptosis.Conclusions: Paclitaxel can induce COX-2 mRNA expression of gastric cancer cell line SGC-7901. P38 signaling pathway inhibitor SB203580 can inhibit the expression. SB203580 could improve paclitaxel-induced apoptosis .P38 signal pathway is one of the possible way involved in the effects of Paclitaxel-induced COX-2 expression on the SGC-7901 cell line.