白细胞介素-1β对结肠癌干细胞迁移及诱导上皮-间质转化的影响  

Effect of interleukin-1βon colon cancer stem cell metastasis and induces epithelial-mesenchymal transition

作　　者：莫波 雍鑫 乔丽娟 杨明 刘阳 徐辉 MO Bo;YONG Xin;QIAO Li-juan;YANG Ming;LIU Yang;XU Hui(Clinical Medical College,Southwest Medical University,Luzhou 646000,Sichuan Province,China;Department of Gastroenterology,The Western Theater General Hospital of Chinese People's Liberation Army,Chengdu 610083,Sichuan Province,China)

机构地区：[1]西南医科大学临床医学院,四川泸州646000 [2]中国人民解放军西部战区总医院消化内科,四川成都610083

出　　处：《中国临床药理学杂志》2021年第21期2901-2904,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金青年基金资助项目(NSFC81702425)。

摘　　要：目的研究白细胞介素-1β(IL-1β)促进结肠癌干细胞转移及要到上皮间质转化的作用机制。方法以原代细胞无血清培养刺激原代细胞向干细胞转化的方法获取干细胞。根据处理方式将结肠癌细胞分为对照组(不处理)和IL-1β组(4 ng·mL^(-1)IL-1β处理)。观察IL-1β处理对结肠癌干细胞转移能力、上皮间质转化以及干细胞相关基因mRNA及蛋白水平的影响。同时根据不同的处理方式将结肠癌细胞分为IL-1β组(IL-1β处理)和shZeb1+IL-1β组(经shZeb1慢病毒感染后IL-1β再处理)。观察结肠癌干细胞相关基因以及EMT相关基因mRNA和蛋白水平变化。结果IL-1β处理后结肠癌干细胞转移数量增多,对照组和IL-1β组的迁移细胞数目分别为(796.33±42.72)和(458.67±20.64),差异有统计学意义(P<0.01)。IL-1β组结肠癌干细胞上皮间质转化细胞数量明显增多,细胞形态由上皮典型的上皮细胞形态向间质细胞形态转化;IL-1β组结肠癌干细胞相关基因mRNA及蛋白表达量改变,B细胞特异的莫洛尼白血病插入位点1基因(Bmi1)、Nestin、E盒结合锌指蛋白(Zeb1)、Zeb2基因及蛋白表达均显著高于对照组。对照组和IL-1β组E-cadherin蛋白表达量分别为0.66±0.09,0.32±0.04,Vimentin蛋白表达分别为0.38±0.04,0.77±0.07,IL-1β组和IL-1β+shZeb1组E-cadherin蛋白表达量分别为0.38±0.04,0.91±0.05,Vimentin蛋白表达量分别为0.76±0.05,0.40±0.06,差异均有统计学意义(均P<0.01)。IL-1β组和shZeb1+IL-1β组Bmi1 mRNA表达分别为1.37±0.10,0.28±0.05,Nestin mRNA表达分别为1.25±0.14,0.21±0.10,Bmi1蛋白表达分别为0.66±0.07,0.31±0.12,Nestin蛋白表达分别为0.71±0.13,0.31±0.12,差异均有统计学意义(均P<0.01)。结论IL-1β可促进结肠癌干细胞转移及诱导上皮-间质转化,其机制与上调Zeb1有关。Objective To investigate the mechanism of interleukin-1β(IL-1β)promoting metastasis and epithelial-mesenchymal transformation of colon cancer stem cells.Methods The primary cells were cultured without serum to stimulate the transformation of primary cells into stem cells.Colon cancer cells were divided into control group(no treatment)and IL-1βgroup(4 ng·mL^(-1)IL-1βtreatment).To observe the effects of IL-1βtreatment on the metastasis,epithelial-mesenchymal transformation and mRNA and protein levels of stem cell-related genes of colon cancer stem cells.According to different treatment methods,colon cancer cells were divided into IL-1βgroup(IL-1βtreatment)and shZ eb1+IL-1βgroup(IL-1βretreatment after shZ eb1 lentivirus infection).The mRNA and protein levels of colon cancer stem cell related genes and EMT related genes were observed.Results The number of metastasis of colon cancer stem cells increased after IL-1βtreatment.The number of migration cells in control group and IL-1βgroup were(796.33±42.72)and(458.67±20.64),respectively,and the difference was statistically significant(P<0.01).In IL-1βgroup,the number of epithelial mesenchymal transformation cells increased significantly,and the cell morphology changed from typical epithelial cell morphology to mesenchymal cell morphology.The mRNA and protein expressions of colon cancer stem cell related genes in IL-1βgroup were changed,and the gene and protein expressions of B lymphoma Mo-MLV insertion region 1 homolog(Bmi1),Nestin,zinc finger E-box-binding protein 1(Zeb1),Zeb2 were significantly higher than those in control group.The expression levels of E-cadherin in control group and IL-1βgroup were 0.66±0.09,0.32±0.04,Vimentin were 0.38±0.04,0.77±0.07,the expression levels of E-cadherin in IL-1βgroup and IL-1β+sh Zeb1 group were 0.38±0.04 and0.91±0.05,Vimentin were 0.76±0.05,0.40±0.06,the differences were statistically significant(all P<0.01).Bmi1 mRNA expression in IL-1βgroup and sh Zeb1+IL-1βgroup were 1.37±0.10 and 0.28±0.05,Nestin mR

关 键 词：结肠癌干细胞 转移 上皮间质转化 白细胞介素-1Β E盒结合锌指蛋白1 

分 类 号：R979.1[医药卫生—药品]