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目的探讨芬戈莫德(FTY720)影响调节性T细胞(Tregs)迁徙与抑制小鼠结肠癌发展的关系。方法灌胃给予结肠癌模型小鼠FTY720,检测Tregs在模型小鼠各组织中的相对比例,以及趋化因子受体CCR4在Tregs的表达量,确定Tregs表达与肿瘤大小的相关性;检测混合细胞培养体系中Tregs的相对比例和CCR4m RNA表达,对比CCR4的表达差异,明确FTY720与Tregs迁徙的相关性。结果 FTY720组瘤质量显著低于模型组(P<0.05),FTY720组Tregs在肿瘤组织局部的比例明显小于模型组(P<0.01),其CCR4+Tregs的比例同样低于模型组(P<0.01);FTY720显著降低Tregs在混合培养体系中的百分比,下调CCR4 m RNA的表达,且呈剂量依赖性。结论 FTY720抑制小鼠结肠癌的发展与影响Tregs的迁徙相关,其机制可能与FTY720下调CCR4在Tregs的表达有关。
Objective To investigate the relationship between the effect of fingolimod (FTY720) on the migration of regulatory T cells (Tregs) and the inhibition of the development of colon cancer in mice. Methods The colon cancer model mice FTY720 were intragastrically administered. The relative proportion of Tregs in the tissues of the model mice and the expression of the chemokine receptor CCR4 in Tregs were determined to determine the correlation between Tregs expression and tumor size. The mixed cells The relative proportion of Tregs and the expression of CCR4m RNA in culture system were compared with that of CCR4 and the correlation between FTY720 and Tregs migration was clarified. Results The tumor mass in FTY720 group was significantly lower than that in model group (P <0.05). The proportion of Tregs in FTY720 group was significantly lower than that in model group (P <0.01), and the proportion of CCR4 + Tregs in FTY720 group was also lower than that in model group ); FTY720 significantly reduced the percentage of Tregs in mixed culture system and down-regulated the expression of CCR4 mRNA in a dose-dependent manner. Conclusion FTY720 inhibits the development of colon cancer in mice and is related to the migration of Tregs. The possible mechanism is that FTY720 may down-regulate the expression of CCR4 in Tregs.