NDRG4通过Wnt/β-catenin信号转导通路抑制卵巢癌细胞的迁移和侵袭能力  

NDRG4 inhibits ovarian cancer cell migration and invasion via Wnt/β-catenin signaling pathway

作　　者：李委佳[1] 贾朝阳[1] 冯书君 刘巍[1] 张顺今 王瑞雪[1] 谭文华[1] Li Weijia;Jia Zhaoyang;Feng Shujun;Liu Wei;Zhang Shunjin;Wang Ruixue;Tan Wenhua(Department of Gynecology and Obstetrics,the Second Affiliated Hospital of Harbin Medical University,Harbin 150001,China)

机构地区：[1]哈尔滨医科大学附属第二医院妇产科

出　　处：《实用肿瘤杂志》2019年第6期497-502,共6页Journal of Practical Oncology

基　　金：黑龙江省卫生计生委科研课题(2016-059)

摘　　要：目的探讨N-myc downstream regulated gene 4(NDRG4)对卵巢癌SKOV3细胞迁移和侵袭能力的影响及其分子机制。方法应用脂质体转染法将NDRG4过表达载体pcDNA3.1-NDRG4质粒(pcDNA3.1-NDRG4质粒组)和空白pcDNA3.1质粒(空白质粒组)转染至SKOV3细胞中。采用实时荧光定量PCR和Western blot法验证NDRG4过表达效果,应用transwell小室法检测细胞迁移和侵袭能力的变化,Western blot法检测卵巢癌细胞中上皮间质转化相关蛋白(E-cadherin、N-cadherin和Vimentin)以及Wnt/β-catenin信号通路相关蛋白(β-catenin和c-myc)的表达水平。结果转染48 h后,与空白质粒组比较,pcDNA3.1-NDRG4质粒组细胞迁移和侵袭能力均下降(P=0.006,P=0.023)。转染72 h后,与空白质粒组比较,pcDNA3.1-NDRG4质粒组E-cadherin表达水平上升(P=0.023),N-cadherin和Vimentin的表达水平均下降(P=0.013,P=0.021)。转染72 h后,与空白质粒组比较,pcDNA3.1-NDRG4质粒组β-catenin和c-myc的表达水平均下降(P=0.035,P=0.006)。结论NDRG4蛋白抑制卵巢癌细胞迁移和侵袭能力,并抑制上皮间质转化过程。该作用可能是通过抑制Wnt/β-catenin细胞信号通路实现。Objective To investigate the effect of N-myc downstream regulated gene 4(NDRG4)on the migration and invasion of ovarian cancer SKOV3 cells,and to explore its possible molecular mechanism.Methods The NDRG4 overexpression vector pcDNA3.1-NDRG4 plasmid(pcDNA3.1-NDRG4 plasmid group)and blank pcDNA3.1 plasmid(blank plasmid group)were transfected into SKOV3 cells by lipofection.qRT-PCR and Western blot were used to verify the overexpression of NDRG4.Transwell assay was used to detect the changes of cell migration and invasion ability.Western blot was used to detect the expression of epithelial-mesenchymal transition proteins(E-cadherin,N-cadherin and Vimentin)and Wnt/β-catenin signal pathway protein(β-catenin and c-myc).Results After 48 h transfection,the cell migration and invasion abilities of the pcDNA3.1-NDRG4 plasmid group were significantly declined compared with the blank plasmid group(P=0.006,P=0.023).After 72 h transfection,the expression level of E-cadherin in the pcDNA3.1-NDRG4 plasmid group was increased(P=0.023)whereas the expression levels of N-cadherin and Vimentin were decreased(P=0.013,P=0.021).Meanwhile the expression levels ofβ-catenin and c-myc in the pcDNA3.1-NDRG4 plasmid group were significantly decreased compared with the blank plasmid group(P=0.035,P=0.006).Conclusion NDRG4 inhibits the migration and invasion of ovarian cancer cells and the process of epithelial-mesenchymal transition by suppressing the Wnt/β-catenin signal pathway.

关 键 词：卵巢肿瘤/病理生理学 基因 肿瘤抑制 上皮细胞/细胞学 信号传导 WNT蛋白质类 肿瘤侵润 细胞运动 肿瘤细胞 培养的 

分 类 号：R737.31[医药卫生—肿瘤] R730.23[医药卫生—临床医学]