IL-18对BALBc小鼠结直肠癌肝转移模型PI3K/AKT信号通路相关蛋白表达水平的影响  

Effects of IL-18 on expression levels of PI3K/AKT signaling pathway-related proteins in colorectal cancer liver metastasis model of BALBc mice

作　　者：关玉峰 贺丽荣 王浩志 GUAN Yu-feng;HE Li-rong;WANG Hao-zhi(Digestive Center,Panyu District Central Hospital,Guangzhou 511400,China)

机构地区：[1]广州市番禺区中心医院消化中心,广东广州511400

出　　处：《解剖学研究》2021年第2期128-132,共5页Anatomy Research

摘　　要：目的探讨白介素18(IL-18)对BALBc小鼠结直肠癌肝转移模型PI3K/AKT信号通路相关蛋白表达水平的影响。方法选取60只BALBc小鼠,采用随机数字表法将小鼠分为:空白对照组、低、中、高剂量IL-18组,每组15只;除空白对照组外各组采用脾内种植法构建结肠癌肝转移小鼠模型,低剂量、中剂量、高剂量IL-18组分别于构建前或构建后注射(20、40和80μg/kg)的IL-18结合蛋白(IL-18BP);检测各组小鼠转移灶大小、数目、质量;采用酶联免疫吸附试验(ELISA)检测各组小鼠血清和腹水中IL-18水平;采用蛋白质印记法及免疫组化检测各组小鼠结直肠癌肝转移组织中E-cadherin、N-cadherin表达;采用蛋白质印记法检测PI3K/Akt信号通路相关蛋白表达情况。结果相比空白对照组,低剂量IL-18组小鼠腹水IL-18水平、血清IL-18水平、N-cadherin阳性率、p-AKT蛋白相对表达、PI3K蛋白相对表达水平显著升高,E-cadherin阳性率显著降低(P<0.05),总AKT蛋白相对表达差异无统计学意义(P>0.05);相比低剂量组,中剂量组小鼠瘤体积、转移灶数量、瘤重、腹水IL-18水平、血清IL-18水平、N-cadherin阳性率、p-AKT蛋白相对表达、PI3K蛋白相对表达水平显著升高且高剂量组上述指标高于中剂量组(P<0.05);相比低剂量组,中剂量组E-cadherin阳性率显著降低,且高剂量组上述指标低于中剂量组(P<0.05),低、中、高白介素18组总AKT蛋白相对表达差异均无统计学意义(P>0.05)。结论 IL-18可以通过激活型PI3K/AKT信号通路促进BALBc小鼠结直肠癌的转移及生长。Objective To explore the effects of IL-18 on the expression levels of PI3K/Akt signaling pathway-related proteins in colorectal cancer(CRC)liver metastasis model of BALBc mice.Methods Sixty BALBc mice were enrolled and divided into blank control group,low-dose,medium-dose and high-dose interleukin 18(IL-18)groups by random number table method,15 cases in each group. Except blank control group,intrasplenic implantation was applied to construct mice models of colon cancer liver metastasis in the other groups. Before or after construction,low-dose,medium-dose and high-dose IL-18 groups were injected with(20 μg/kg,40 μg/kg,80 μg/kg)IL-18 binding protein(IL-18 BP),respectively. The size,number and quality of metastases in each group were detected. The levels of IL-18 in serum and ascites in each group were detected by enzyme-linked immunosorbent assay(ELISA). The expression of E-cadherin and N-cadherin in CRC liver metastasis tissues of each group was detected by Western blot and immunohistochemistry. The expression of PI3 K/Akt signaling pathway-related proteins was detected by Western blot.Results Compared with blank control group,levels of IL-18 in ascites and serum,positive rate of N-cadherin,relative expression levels of of p-AKT and PI3K proteins were significantly increased,while positive rate of E-cadherin was significantly decreased in low-dose IL-18 group(P<0.05),and there was no significant difference in the relative expression of total AKT protein(P>0.05). Compared with the low-dose IL-18 group,tumor volume,number of metastases,tumor weight,levels of IL-18 in ascites and serum,positive rate of N-cadherin,relative expression levels of of p-AKT and PI3K proteins were significantly increased in medium-dose IL-18 group,which were higher in high-dose IL-18 group than medium-dose IL-18 group(P<0.05). Compared with the low-dose IL-18 group,positive rate of E-cadherin was significantly decreased in medium-dose IL-18 group,which was lower ub high-dose IL-18 group than medium-dose IL-18 group(P<0.05). There was n

关 键 词：结直肠癌 白细胞介素18 肿瘤肝转移模型 PI3K/AKT通路 

分 类 号：R735.34[医药卫生—肿瘤] R-332[医药卫生—临床医学]