胰岛素样生长因子-2通过介导胃癌大鼠Treg免疫活性破坏机体免疫功能的促癌作用研究  

Tumor-promoting effects of insulin-like growth factor 2 on gastric cancer by mediating Treg immunocompetence in rats

作　　者：胡玲莉 HU Lingli(Department of Gastroenterology,Wuhan Jinyintan Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430000,China)

机构地区：[1]华中科技大学同济医学院附属武汉市金银潭医院消化科,430000

出　　处：《免疫学杂志》2024年第5期464-468,共5页Immunological Journal

摘　　要：目的研究胰岛素样生长因子-2(IGF-2)通过介导胃癌大鼠Treg免疫活性破坏机体免疫功能的促癌作用。方法选取健康SD雄性大鼠40只,于右侧腋窝皮下接种胃癌SGC-7901细胞株建立胃癌模型,随机分为模型组、低剂量组(25μg/kg IGF-2)、中剂量组(50μg/kg IGF-2)及高剂量组(100μg/kg IGF-2),每组10只,均连续给药14 d。观察记录4组大鼠瘤体积、瘤质量以及胸腺、脾脏重量,计算抑瘤率以及胸腺、脾脏指数。流式细胞仪检测血液Treg、Th17水平,采用苏木精-伊红染色法观察肿瘤组织病理学形态,TUNEL检测胃癌细胞凋亡,采用蛋白印迹法检测4组大鼠肿瘤组织PI3K/Akt信号通路表达情况。结果各剂量组脾脏指数、胸腺指数均低于模型组,且随着给药剂量的增加,均呈明显降低趋势,而促瘤率均呈增加趋势(P<0.05)。各剂量组肿瘤组织细胞凋亡率均低于模型组,随着给药剂量的增加,凋亡率均呈降低趋势(P<0.05)。随着IGF-2剂量的增加,Treg、Th17、Treg/Th17均明显增加(P<0.05)。不同剂量组的p-Akt、CYP19A1蛋白表达水平高于模型组,随着给药剂量的增加,p-Akt、CYP19A1蛋白表达水平呈明显增加趋势(P<0.05)。结论IGF-2可促进胃癌大鼠肿瘤生长,其作用机制可能为通过上调PI3K/Akt信号通路,破坏Treg/Th17细胞免疫功能平衡,从而抑制肿瘤细胞凋亡。To investigate the promoting effect of insulin-like growth factor 2(IGF-2)on cancer by mediating Treg immune activity in rats with gastric cancer,total of 40 healthy male SD rats were selected and subcutaneously inoculated with gastric cancer SGC-7901 cell line in the right axilla to establish a gastric cancer model.The model rats were randomly divided into a model group,a low-dose group(25μg/kg IGF-2),a medium dose group(50μg/kg IGF-2)and a highdose group(100μg/kg IGF-2),with 10 rats in each group.After continuous 14 days of administration,the tumor volume,tumor mass,thymus and spleen weight of rats in the 4 groups were observed and recorded for calculate tumor inhibition rate,thymus index and spleen index.Furthermore,Treg and Th17 levels in blood were detected by flow cytometry,tumor histopathological morphology was observed by hematoxylin-eosin staining,the apoptosis of gastric cancer cells was detected by TUNEL,and the expression of PI3K/Akt signaling pathway in tumor tissues of rats in 4 groups were detected by Western blotting.Data showed that the spleen index and thymus index of each dose group were lower than those of the model group,and showed a significant decreasing trend with the increase of the dosage,while the tumor promotion rate showed an increasing trend(P<0.05).Compared with the model group,IGF inhibited the apoptosis rate of cancer cells in each dose group in a dose-dependent manner(P<0.05).With the increase of IGF-2 dose,Treg,Th17 and Treg/Th17 all increased significantly(P<0.05)in IGF groups.The expression levels of p-Akt and CYP19A1 proteins in different dose groups were higher than those in the model group.As the dosage increased,the expression levels of p-Akt and CYP19A1 proteins showed a significant increase trend(P<0.05).Taken together,IGF-2 can promote tumor growth in gastric cancer rats,and its mechanism may relate to disrupting the immune function balance of Treg/Th17 cells through up-regulation of PI3K/Akt signaling pathway,thus inhibiting tumor cell apoptosis.

关 键 词：胰岛素样生长因子-2 胃癌 TREG细胞 免疫功能 促癌 

分 类 号：R392.11[医药卫生—免疫学]