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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IC50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,TopoⅡmRNA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 study the effect of celecoxib on chemosensitivity of T cell lymphoma cells and to explore its mechanism. Methods: MTT assay was used to determine the effect of different concentrations of celecoxib on the proliferative activity of Jurkat and Hut78 cells at 24, 48 and 72 h, respectively. MTT assay was used to detect the chemotherapeutic drugs (cisplatin, DDP) Epirubicin (EPI) and vincristine (VCR)] in combination with celecoxib on the proliferation of Jurkat and Hut78 cells; IC50 values were calculated; and celecoxib and chemotherapeutic drugs were detected by flow cytometry On the apoptosis of Jurkat and Hut78 cells. The effects of celecoxib on the expression of MDR1, MRP1, LRP and TopoⅡ in Jurkat and Hut78 cells were detected by Real-time PCR and Western blotting respectively. Results: Celecoxib could inhibit the proliferation of Jurkat and Hut78 cell lines, and could significantly enhance the killing effect of chemotherapeutic drugs on Jurkat and Hut78 cells. In celecoxib treated Jurkat and Hut78 cells (P <0.01). The expression of TopoⅡmRNA and protein were significantly increased in Jurkat and Hut78 cells co-cultured with celecoxib, while the mRNA and protein expressions of MDR1, MRP1 and LRP were significantly decreased (P <0.01) P <0.05). Conclusion: Celecoxib can enhance the sensitivity of T lymphoma cells to chemotherapeutic drugs by regulating the expression of drug-resistance-related genes. Therefore, Celecoxib has a good application prospect in the clinical treatment of T-cell lymphoma.