目的： 研究塞来昔布对T细胞淋巴瘤细胞化疗敏感性的影响，并探讨其作用机制。方法： MTT法检测不同浓度塞来昔布分别作用24、48和72 h，对T细胞淋巴瘤细胞株Jurkat和Hut78增殖活性的影响；MTT法检测化疗药物\[顺铂（cisplatinum，DDP）、表柔比星（epirubicin, EPI)及长春新碱（vincristine，VCR）\]联合塞来昔布对Jurkat和Hut78细胞增殖活性的影响；并计算IC50值；流式细胞术检测塞来昔布联合化疗药对Jurkat和Hut78细胞凋亡水平的影响； Real-time PCR及Western blotting技术分别从mRNA及蛋白水平检测塞来昔布对Jurkat和Hut78细胞表达MDR1、MRP1、LRP及TopoⅡ的影响。结果： 塞来昔布对T细胞淋巴瘤细胞株Jurkat和Hut78增殖活性具有一定抑制作用，且可明显增强化疗药物对Jurkat和Hut78细胞的杀伤作用；在塞来昔布作用下Jurkat和Hut78细胞的凋亡水平明显增加（P<0.01）；与塞来昔布共培养的Jurkat和Hut78细胞，TopoⅡ mRNA和蛋白的表达水平均明显增加，而MDR1、MRP1、LRPmRNA及蛋白的表达水平均明显下降（P<0.05）。结论：塞来昔布可通过调控耐药相关基因的表达而增强T淋巴瘤细胞对化疗药物的敏感性，因此在T细胞淋巴瘤的临床治疗中具有良好应用前景。

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 IC50 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<001). 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.

河北省医学科学研究重点课题资助项目（ No. 20150305）