Cyclooxygenase-2Regulates Bcl-2Protein Expression Through JNK Signal Pathway

Objective:Gastric cancer is one of common malignant tumors in china.Currently,drug resistance is the most likely reasons for the poor effect ofchemotherapy for advanced gastric cancer. Overexpression of cyclooxygenase-2(COX-2) and Bcl-2has been detected in advanced gastric cancer in manyresearchs. Unfortunately it always means drug resistance and Poor prognosis.Although COX-2and Bcl-2are closely related to each other, the exact mechanismof COX-2in tumors has not been well understood. Accordingly, we selectedgastric cancer cell line BGC-823for this study. To observe the effects of COX-2on Bcl-2expression and activity, we did comparative analyses after treatment withvarious drugs(low doses of paclitaxel,NS398,SP600125) in BGC-823.It willprovide a theoretical basis for founding a new Chemotherapy-sensitive target.Methods: Advanced gastric cancer BGC-823was exposed to low doses ofpaclitaxel and then we separated gastric cancer cells into two groups depending onthe protein levels of COX-2. The protein levels of JNK and p-JNK was detectedafter treatment with NS398, a specific COX-2inhibitor. The protein levels of Bcl-2was also detected after treatment with SP600125, a specific JNK inhibitor.Results: We found COX-2and Bcl-2was expressed in normal gastric cancer cells.However，COX-2and Bcl-2protein expression was up-regulated with prolongpaclitaxel treatment time. Expression level of p-jnk in experiment grounp was significantly lower than control group. While addingthe COX-2specific inhibitor NS398, and low-dose paclitaxel in theexperimental group, p-JNK protein expression level was being thehighest of all. Expression level of Bcl-2protein was up-regulatedin both experimental group and control group When JNK channelblocked by its specific inhibitor SP600125.Conclusions：Overexpressed COX-2positively regulates Bcl-2expression viaJNK Supression. It may have significance in clinical cancer therapy.