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目的研究塞来昔布对T细胞淋巴瘤Jurkat细胞株化疗敏感性的影响,并探讨其作用机制。方法 MTT法检测表柔比星联合塞来昔布对Jurkat细胞增殖活性的影响,并计算IC_(50)值;流式细胞术检测表柔比星联合塞来昔布对Jurkat细胞凋亡水平的影响;Western blot检测塞来昔布对Jurkat细胞株表达P-gp、MRP1、LRP及TopoⅡ蛋白水平的影响;构建Jurkat细胞株裸鼠移植瘤模型,分为模型对照组、单独塞来昔布组、单独表柔比星组及塞来昔布表柔比星组,治疗后引颈处死裸鼠,剥离瘤组织,检测其质量、体积、瘤组织细胞凋亡率,同时检测瘤组织表达MDR1、MRP1、LRP及TopoⅡ的水平。结果表柔比星联合塞来昔布对T细胞淋巴瘤细胞株Jurkat增殖活性具有明显抑制作用,同时表柔比星的IC_(50)值明显减低(P<0.05),Jurkat细胞的凋亡水平也较对照组明显增加(P<0.01);与塞来昔布共培养的Jurkat细胞表达TopoⅡ蛋白的水平明显增加,而表达MDR1、MRP1、LRP蛋白的水平均明显下降(P<0.05);联合塞来昔布可明显增强表柔比星对Jurkat瘤组织的抑制作用,并可明显下调瘤组织MDR1、MRP1、LRP的表达水平,上调TopoⅡ的表达水平。结论塞来昔布可通过调控耐药相关基因的表达而增强Jurkat细胞化疗敏感性,因此提示该药在T细胞淋巴瘤的临床治疗中具有广泛前景。
Objective To study the effect of celecoxib on chemosensitivity of T cell lymphoma Jurkat cell line and its mechanism. Methods MTT assay was used to detect the proliferation of Jurkat cells induced by epirubicin combined with celecoxib. IC 50 values were calculated. Flow cytometry was used to detect the apoptosis of Jurkat cells induced by epirubicin and celecoxib Western blot was used to detect the effect of celecoxib on the expression of P-gp, MRP1, LRP and TopoⅡ in Jurkat cells. The Jurkat cell xenograft model was established and divided into model control group, celecoxib group , Epirubicin alone and celecoxib epirubicin group. After treatment, the nude mice were euthanized and the tumor tissue was dissected. The mass, volume and the apoptosis rate of the tumor tissue were detected. At the same time, the expression of MDR1, MRP1 , LRP and Topo II levels. Results Epirubicin and celecoxib significantly inhibited the proliferation of Jurkat cells, and the IC 50 of epirubicin was significantly decreased (P <0.05). The apoptosis of Jurkat cells (P <0.01). The expression of TopoⅡprotein in Jurkat cells co-cultured with celecoxib was significantly increased, while the levels of MDR1, MRP1 and LRP protein were significantly decreased (P <0.05) Celecoxib significantly enhanced the inhibition of epirubicin on Jurkat tumor tissues, and significantly down-regulated the expression of MDR1, MRP1, LRP and up-regulated TopoII expression. Conclusion Celecoxib can enhance chemosensitivity of Jurkat cells by regulating the expression of drug resistance-related genes, suggesting that this drug has broad prospects in the clinical treatment of T-cell lymphoma.