IL-1β通过上调CDC42/NF-κB信号通路促进胃癌细胞的增殖、迁移及侵袭  

IL-1β promotes proliferation, migration and invasion of gastric cancer cells by up-regulating CDC42/NF-κB signaling pathway

作　　者：许春蕾[1] 李娜[1] 汤旭山[1] XU Chun-lei;LI Na;TANG Xu-shan(Department of Gastroenterology,Tumor Hospital Affiliated to Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]新疆医科大学附属肿瘤医院消化内科,乌鲁木齐830011

出　　处：《现代免疫学》2020年第6期441-445,453,共6页Current Immunology

基　　金：新疆维吾尔自治区自然科学基金(2018D01C217)。

摘　　要：本研究主要探讨炎性因子IL-1β对胃癌细胞BGC-823中细胞分裂周期蛋白42(cell division cycle protein 42,CDC42)表达及胃癌细胞增殖、迁移及浸润能力的影响,并初步探究其相关的作用机制。首先应用炎性因子IL-1β刺激BGC-823细胞24 h,采用实时荧光定量PCR及Western blotting观察细胞中CDC42 mRNA及蛋白表达变化,应用瞬时转染技术将si-CDC42-1和si-CDC42-2转染入BGC-823细胞内进行沉默CDC42的表达,再次利用实时荧光定量PCR及Western blotting检测转染后细胞内CDC42 mRNA及蛋白表达水平。采用CCK-8细胞增殖试验、细胞划痕试验、Transwell试验观察沉默CDC42后胃癌细胞在增殖、迁移及浸润方面的变化。应用实时荧光定量PCR和Western blotting检测NF-κB信号通路中关键分子基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)、Slug mRNA及蛋白的表达变化。结果显示,胃癌细胞BGC-823经炎性因子IL-1β刺激后,其CDC42 mRNA及蛋白表达量显著高于正常对照组(P<0.05);si-RNA转染BGC-823细胞后,si-CDC42-1组和si-CDC42-2组BGC-823细胞中CDC42 mRNA及蛋白表达量显著低于正常对照组(P<0.05);si-CDC42-1组和si-CDC42-2组BGC-823细胞与阴性对照(negative control,NC)组比较,其24、48和72 h增殖、迁移及浸润能力均显著降低(P<0.05);且沉默BGC-823细胞内CDC42表达后,si-CDC42-1组和si-CDC42-2组细胞内NF-κB信号通路中关键分子MMP-9、Slug mRNA及蛋白表达量均较NC组显著降低(P<0.05)。提示炎性因子IL-1β可促进胃癌细胞BGC-823中CDC42的表达,且沉默CDC42表达后可明显抑制胃癌细胞的增殖、迁移及浸润,这一现象可能是通过NF-κB信号通路发挥作用的。The purpose of this study was to investigate the effect of IL-1β on the expression of cell division cycle protein 42(CDC42) in BGC-823 cells and its proliferation, migration and infiltration, and to explore its mechanism. After 24 hours stimulationof BGC-823 cells by IL-1β, the expression of CDC42 mRNA and protein was observed by real time fluorescence quantification PCR and Western blotting. The expression of CDC42 was silenced by transient transfection of si-CDC42-1/2 into BGC-823 cells, and then the expression of CDC42 mRNA and protein was detected by real time fluorescence quantification PCR and Western blotting. CCK-8, scratch test and Transwell test were used to observe the proliferation, migration and infiltration of gastric cancer cells after CDC42 silencing. Real time fluorescence quantification PCR and Western blotting were used to detect the mRNA and protein expression of matrix metalloproteinase 9(MMP-9) and slug in NF-κB signaling pathway. The results showed that the expression of CDC42 mRNA and protein in BGC-823 cells stimulated by IL-1β was significantly higher than that in the control group(P<0.05). The expression of CDC42 mRNA and protein in BGC-823 cells in si-CDC42-1 group and si-CDC42-2 group was significantly lower than that in the control group(P<0.05). The proliferation, migration and invasion of BGC-823 cells in si-CDC42-1 group and si-CDC42-2 group were significantly lower than those in the negative control(NC) group(P<0.05). After down regulating the expression of CDC42 in BGC-823 cells, the mRNA and protein expression of MMP-9 and Slug, the key molecules of NF-κB signaling pathway, in si-CDC42-1 group and si-CDC42-2 group were significantly lower than those in the NC group(P<0.05). In conclusion, the inflammatory factor IL-1β could promote the expression of CDC42 in BGC-823 cells, and silencing the expression of CDC42 could significantly inhibit leading to the proliferation, migration and infiltration of gastric cancer cells. The effect of IL-1β could be mediated by NF-κB signa

关 键 词：白细胞介素1Β 细胞分裂周期蛋白42 核因子ΚB 胃癌 

分 类 号：R735.2[医药卫生—肿瘤]