Experimental Study Of The Role And Mechanism About Cyclooxygenase-2Expression In NK/T Cell Lymphoma Chemotherapy Drug Resistance

Objective Cyclooxygenase-2(cyclooxygenase-2, COX-2) is an important rate limiting enzyme in the process of prostaglandin synthesis, play an important role in the development of tumor. Research shows that: Cyclooxygenase-2expression can serve as a predictive factor for poor treatment response and unfavorable prognosis in patients with extranodal NK/T-cell lymphoma, nasal type.suggesting that COX-2play an important role in this type of lymphoma tumor resistance to chemotherapy.the important reason of the tumor resistance to chemotherapy is the tolerance of on apoptosis induced. The changes of apoptosis signal pathway and apoptosis related molecules will cause the cell apoptosis resistance. The phosphatidylinositol-3kinase/protein kinase B (PI3K/Akt) activation signal pathway is considered one of the major mechanisms of tumor cell apoptosis; influence the sensitivity of tumor cells to chemotherapy. In other tumor cells, blocking the PI3K/Akt signaling pathway by PI3K inhibitor, the resistance of cancer cells to chemotherapeutic drugs can be weakened. It was aimed to investigate the possible mechanism of chemotherapy drug resistance induced by COX-2expression in NK/T cell lymphoma. This study used chemotherapy drug epirubicin induced NK/T lymphoma cell line YTS to obtain high expression cell line COX-2and group study, detect the expression of p-Akt, Bax, Bcl-2, Mcl-1, and cell survival rate. To investigate the role of p-Akt signal pathway and cell apoptosis pathway in chemotherapy resistance and the possible mechanism in the igh expression of COX-2in NK/T cell lymphoma.Methods:the effects of epirubicin on NK/T cells growth was assessed by MTS assay, and so did the effects of COX-2selective inhibitor celecoxib and Akt pathway inhibitor LY294002.The effect of epirubicin on the COX-2expression was detected by Western blotting. Choose high COX-2expression of cell lines induced by epirubicin in to group study.every group dealed with epirubicin, epirubicin and celecoxib20umol/L, epirubicin and celecoxib20umol/L withLY29400225umol/L. western blotting detect the erxpression of Akt, p-Akt, Bax, Bcl-2, Mcl-1. MTS detect cell growth, Flow cytometry detect cell apoptosis.Results epirubicin, celecoxib and LY294002had the cellular toxicity on YTS cell line growth in a dose-dependent manner. When the dose of epirubicin increased, the expression of COX-2showed rising trend in YTS cell line. Compared with control cell, COX-2-overexpressing cells have more tolerance of epirubicin., and have the more expression of p-Akt, Bcl-2, Mcl-1, less expression of Bax. COX-2-overexpressing cells add epirubicin.COX-2-overexpressing cells add epirubicin and celecoxib (20umol/L), COX-2-overexpressing cells add epirubicin combined with celecoxib (20umol/L) and LY294402(25umol/L). comparing the three groups, Cell survival rate falling gradually, cell apoptosis rate increased gradually. Bax expression increased gradually. Expression of Bcl-2, Mcl-1, and p-Akt reduced gradually.Conclusion epirubicin can induce NK/T lymphoma cell lines YTS COX-2expression. The expression of p-Akt can suppress by COX-2inhibitor celecoxib. High expression of COX-2cell lines may through the p-signaling pathway mediated apoptosis pathway to improve tolerance of epirubicin.