Celecoxib promotes drug sensitivity of T cell lymphoma to chemotherapy
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Abstract:
Objective:To investigate the effect of celecoxib on chemotherapy sensitivity of T cell lymphoma and the possible mechanism. Methods:The proliferation activities of Jurkat and Hut78 cell lines treated with celecoxib at different concentrations for 24, 48 and 72 h were detected by MTT method. The inhibition effect of chemotherapy drugs \[cisplatinum(DDP), epirubicin (EPI), and vinblastine(VCR)\] associated with celecoxib at different doses on the proliferation of Jurkat and Hut78 cell lines was also detected using MTT method, meanwhile, the IC50 value was calculated. The apoptotic rates of Jurkat and Hut78 cells co-cultured with different chemotherapy drugs associated with celecoxib at different doses were analyzed by Flow Cytometry. Meanwhile, the effect of celecooxib on the expression of MDR1, MRP1, LRP and TopoⅡ at the level of mRNA and protein in Jurkat and Hut78 cells were investigated by Real-time PCR and Western blotting respectively. Results: After the treatment of celecoxib, the proliferation activity of Jurkat and Hut78 cells was inhibited in a dose-and time-dependent manner, and the killing effect of chemotherapy drugs on Jurkat and Hut78 cells was also obviously enhanced (P<0.05); in addition, the apoptotic rate of Jurkat and Hut78 cells was significantly elevated(P<001). The results of Real-time PCR and Western blotting showed that the expressions of MDR1, MRP1 and LRP were down-regulated and TopoⅡ was up-regulated at both mRNA and protein levels in Jurkat and Hut78 cell lines treated with celecoxib at different doses, compared with control group (P<0.05). Conclusion:Celecoxib can enhance the chemotherapy sensitivity of T lymphoma cells by regulating the expression of multidrug resistance(MDR) related genes; Thus, it has a wide application prospect in the clinical treatment of T cell lymphoma.
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Project supported by the Medical Scientific Research Key Program of Hebei Province (No. 20150305)