摘要
目的探讨局部湿热联合微波消融对乳腺癌荷瘤小鼠脾细胞中CD4+CD25+调节性T细胞(Tregs)比例和功能的影响。方法小鼠随机分为荷瘤组、局部湿热/微波消融处理组和局部湿热联合微波消融处理组共4组,每组12只。先建立小鼠乳腺癌实验动物模型,分别进行局部湿热、微波消融或局部湿热联合微波消融处理。用FACS检测脾细胞中Tregs的比例变化;real-time PCR检测Foxp3 mRNA水平;FACS检测CTLA-4和GITR的表达;ELISA法检测TGF-β和IL-10的含量;增殖抑制实验观察CD4+CD25-T细胞体外增殖。结果与单一局部湿热处理组和微波消融处理组相比,Tregs在局部湿热联合微波消融处理组中的比例显著降低(P<0.05)。并且,Tregs细胞的Foxp3、CTLA-4和GITR的表达也明显降低(P<0.05),同时TGF-β和IL-10的分泌及抑制功能也显著削弱(P<0.05)。结论湿热联合微波消融可以较单一治疗方法更有效的抑制肿瘤生长,这与其降低CD4+CD25+调节性T细胞的比例和功能密切相关。
Objective To investigate the effects of wet hyperthermia combined with microwave ablation on the pro- portion and function of CD4 ＋ CD25 ＋ regulatory T cell in animal model of mouse mammary carcinoma and explore its significance. Methods An experimental model of mouse mammary carcinoma was established and then treated with microwave ablation on day 14. Local wet hyperthermia was also performed. The proportion of CIM ＋ CD25 ＋ regula- tory T cells （Tregs） in splenocytes was analyzed by FACS. The relative expression of Foxp3, as well as the expres- sion of CTLA-4 and GITR, on Tregs was determined by real-time PCR assay and FACS respectively. Moreover, the secretion of TGF-β and IL-10 from Tregs also were detected by ELISA. In addition, the suppressive capacity of Tregs on CD4 ＋ CD25 - T cell was also examined by MTY assay. Results The proportion of Tregs in wet hyperther- mia combined with microwave ablation treated group decreased significantly compared with that in wet hyperthermia or microwave ablation treated alone group （P 〈 0. 05 ）. Moreover, the expression level of Foxp3 on Tregs decreased significantly （P 〈 0. 05）. Furthermore, the expression of CTLA4 and GITR, as well as the secretion of TGF-13 and IL- 10, on Tregs also obviously decreased （P 〈 0. 05）. Finally, the suppressive capacity of Tregs on the proliferation of CD4 ＋ CD25 - T cells were also significantly impaired （ P 〈 0. 05 ）. Conclusions Wet hyperthermia combined with microwave ablation os more effective than single wet hyperthermia or microwave ablation as a mono-therapy alone on the function of Tregs, which may be closely related to the enhanced suppression of tumor growth.
出处
《基础医学与临床》
CSCD
2015年第9期1188-1193,共6页
Basic and Clinical Medicine
基金
国家自然科学基金(31370918)
贵州省科技厅联合基金(黔科合J字LKZ[2013]24号)
贵州省卫生厅项目(D-348)
