肺积方联合化疗对Lewis肺癌移植小鼠免疫逃逸相关细胞因子及CD_4^+ CD_(25)^+ Treg细胞的影响

Experimental Research on influence of Feiji Formula combined with Chemotherapy on immune escape related factors and CD_4^+ CD_(25)^+ Treg Cells of Transplanted Lewis Lung Cancer in mice

目的:通过观察肺积方联合化疗对Lewis肺癌移植小鼠肿瘤生长情况及脾脏CD4+ CD25+ Treg细胞、IL-2、IL-4、IL-10、TNF-β、IFN-r变化的影响,探讨肺积方联合化疗抗肺癌免疫逃逸的作用机制,为肺积方的临床应用提供客观依据。方法:采用随机对照研究方法,将64只Lewis肺癌移植小鼠经随机分为对照组、化疗组、肺积组、综合组(肺积方联合化疗),并分别以肺积方、肺积方联合DDP、DDP药物干预,观察小鼠瘤体变化,并以ELISA法检测小鼠外周血细胞因子IL-2、IL-4、IL-10、TNF-β、IFN-r变化,以流式细胞术检测小鼠脾脏CD4+ CD25+ Treg细胞含量。结果:化疗组、肺积组、综合组瘤体、瘤重均小于对照组(P<0.05),肺积组瘤体、瘤重大于化疗组(P<0.05),综合组瘤体、瘤重均小于化疗组和肺积组(P<0.01);综合组IL-2、IL-4水平明显高于其他3组(P<0.05),综合组IL-10、IFN-r、TNF-β水平低于其他3组(P<0.05),肺积组IL-2、IL-4、TNF-β水平与化疗组比较无差异(P>0.05),肺积组IL-10、IFN-r水平高于化疗组(P<0.05);对照组、化疗组、肺积组、综合组第7天脾脏CD4+ CD25+ Treg细胞占CD4+T细胞比值无差异(P>0.05);第14天对照组脾脏CD4+ CD25+ Treg细胞占CD4+T细胞比值仍明显高于其他3组(P<0.05);综合组第14天脾脏CD4+ CD25+ Treg细胞占CD4+T细胞比值明显低于化疗组及肺积组(P<0.01);化疗组脾脏CD4+ CD25+ Treg细胞占CD4+T细胞比值低于肺积组(P<0.05)。结论:肺积方联合化疗具有抗Lewis肺癌移植小鼠肿瘤生长的作用,此种作用与其下调CD4+ CD25+ Treg细胞含量,上调IL-2、IL-4,下调IL-10、TNF-β相关。

Objective ：To investigate the mechanism of Feiji Formula combined with chemotherepy in modulating im mune evasion by observing the tumor body and the level of CD＋4 CD＋25 Treg in mice spleen,and levels of IL- 2,IL -4, IL - 10, TNF - β and 1FN - r in mice with transplanted Lewis lung cancer. Methods ： It was a prospective, randomized, paral- lel - control study. 64 mice with transplanted Lewis lung cancer were randomly divided into chemotherapy group, control group, Feiji Formula group and comprehensive treatment group. The variations of IL - 2, IL - 4, IL - 10, TNF - β and IFN - r of blood and the variation of CD4＋ CD25＋ Treg in spleen of mice among four groups were recorded and evaluated, at the same time the variations of volume and weights of tumor among four groups were compared. Results：The volume and weights of tumor in chemotherapy group, Feiji Formula group and comprehensive treatment group were less than those in control group（ P 〈 0.05 ）. The volume and weights of tumor in Feiji Formula group were more than those in chemotherapy group（P 〈 0.05）. The volume and weights of tumor in comprehensive treatment group were less than those in Feiji For mula group and chemotherapy group（ P 〈 0.01 ）. The levels of IL- 2 and IL- 4 in comprehensive treatment group were higher than those of other groups（ P 〈 0.05 ）. The levels of IL - 10, IFN - r and TNF - 13 of comprehensive treatment group were lower than those of other groups（ P 〈 0.05 ）. There was no difference between Feiji Formula group and chemo- therapy group in the levels of IL - 2, IL - 4 and TNF - β（ P 〉 0.05 ）. The levels of IL - 10 and IFN - r in Feiji Formula group were higher than those in chemotherapy group（P 〈0.05）. There was no difference of the ratio（ CD＋4 CD＋25 Treg,/ CD4＋ T of spleen） among four groups （ P 〉 0.05 ） on 7th day. The ratio in control group was higher than that in other groups （ P 〈 0.05 ）. The ratio in comprehensive treatment group was lower than that in other groups（P 〈 0.01 ）. The ratio in chemotherapy group was lower than that in Feiji Formula group（ P 〈 0.05 ）. Conclusions：Feiji Formula combined with chemotherapy can suppress Lewis lung cancer by improving the levels of IL - 2 and IL - 4 and suppressing the levels of IL - 10 and TNF - βand CD＋4 CD＋25 Treg .