IGF-2通过调控Treg/Th17免疫平衡促进小鼠结肠癌细胞移植瘤生长  

IGF-2 promotes the growth of mouse colon cancer xenografts by regulating Treg/Th17 immune balance

作　　者：周红见 柯超 蒋斌 谢兴旺 ZHOU Hongjian;KE Chao;JIANG Bin;XIE Xingwang(Department of Gastroenteroabdominal Wall and Hernia Surgery,Wuhan Third Hospital,Wuhan 430061,China)

机构地区：[1]武汉市第三医院胃肠腹壁与疝外科,430061

出　　处：《免疫学杂志》2023年第3期255-261,共7页Immunological Journal

基　　金：汉市医学科研项目(WX20D26)。

摘　　要：目的探讨胰岛素样生长因子-2(IGF-2)对结肠癌荷瘤小鼠Treg免疫活性的影响。方法将24只Balb/c小鼠左侧腋部皮下注射小鼠结肠癌细胞CT26制备结肠癌荷瘤小鼠模型,并随机分为对照组(生理盐水)和IGF-2低、中、高浓度组(25μg/kg、50μg/kg、100μg/kg IGF-2)。检测胸腺指数和脾脏指数,酶联免疫(ELISA)法检测血清IL-10、IL-18、TGF-β1、IFN-γ水平,流式细胞仪检测血液Treg、Th17细胞比例,瘤组织称质量、计算小鼠促瘤率,TUNEL染色检测瘤组织细胞凋亡率,Western blot法检测瘤组织中Ki67、Caspase-3蛋白表达。结果与对照组相比,IGF-2低、中、高浓度组结肠癌荷瘤小鼠血清IL-10、TGF-β1水平、血液Treg、Th17、Treg/Th17细胞比例、促瘤率及瘤组织中Ki67蛋白水平显著升高(P<0.05),血清IL-18、IFN-γ水平、胸腺指数和脾脏指数及瘤组织细胞凋亡率、Caspase-3蛋白水平显著降低(P<0.05);随着IGF-2浓度的升高,结肠癌荷瘤小鼠血清IL-10、TGF-β1水平、血液Treg、Th17、Treg/Th17细胞比例、促瘤率及瘤组织中Ki67蛋白水平逐渐升高(P<0.05),血清IL-18、IFN-γ水平、胸腺指数和脾脏指数及瘤组织细胞凋亡率、Caspase-3蛋白水平逐渐降低(P<0.05)。结论IGF-2能发挥促癌作用,其机制可能与其能介导结肠癌荷瘤小鼠Treg/Th17细胞比例失衡,破坏机体免疫功能有关。To investigate the effect of insulin-like growth factor-2(IGF-2)on Treg/Th17 immunobalance in colon cancer tumor-bearing mice,total of 24 Balb/c mice were injected mouse colon cancer cell CT26 on the left axillary subcutaneously to prepare colon cancer tumor-bearing mouse models,and then randomly divided into control group(physiological saline),low IGF-2(25μg/kg),medium IGF-2(50μg/kg)and high IGF-2(100μg/kg)groups,with 6 mouse in each group.Thymus index and spleen index were calculated;the serum IL-10,IL-18,TGF-β1,IFN-γlevels were detected by enzyme-linked immunoassay(ELISA);the proportion of Treg and Th17 cells in the blood were detected by flow cytometry;the tumor tissue was weighed and the tumor promotion rate of mice was calculated.Furthermore,TUNEL staining was used to detect the apoptosis rate of tumor tissue cells,while Western blot method was used to detect the expression of Ki67 and Caspase-3 proteins in tumor tissues.Compared with the control group,the serum IL-10 and TGF-β1 levels,the proportion of Treg,Th17,Treg/Th17 cells in the blood,the tumor promotion rate and the tumor tissues Ki67 protein level were significantly increased in the IGF-2 low,medium and high concentration groups(P<0.05),while the serum IL-18,IFN-γlevels,thymus index and spleen index,tumor cell apoptosis rate,and Caspase-3 protein level were significantly reduced(P<0.05).With the increase of IGF-2 concentration,the serum IL-10 and TGF-β1 levels,the proportion of Treg,Th17,Treg/Th17 cells in the blood,the tumor promotion rate and the tumor tissues Ki67 protein levels increased gradually(P<0.05),and the serum IL-18,IFN-γlevels,thymus index and spleen index,tumor cell apoptosis rate,and Caspase-3 protein level reduced gradually(P<0.05).In conclusion,IGF-2 plays a role in promoting cancer,and the mechanism may be related to its ability to mediates imbalance of Treg/Th17 cells in colon cancer-bearing mice,and to destroy the immune function of the body.

关 键 词：胰岛素样生长因子-2 结肠癌 荷瘤小鼠 Treg/Th17 

分 类 号：R735.3[医药卫生—肿瘤]