抑制SOD1调节上皮间质转化抑制鼻咽癌细胞迁移  

Suppression of Epithelial Mesenchymal Transition and Metastasis in Nasopharyngeal Carcinoma via SOD1 Inhibition

作　　者：付兰燕 邓丽文[1] 戴婷[1] 蒋利玲[2] 龚青[1] 李帅[1] FU Lan-yan DENG Li-wen DAI Ting JIANG Li-ling GONG Qing LI Shuai(Department of Biochemistry Immunology Institute, Guangzhou Medical University, Guangzhou 511436, China)

机构地区：[1]广州医科大学生物化学教研室,广东广州511436 [2]广州医科大学免疫研究所,广东广州511436

出　　处：《中山大学学报（医学科学版）》2017年第1期42-48,共7页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广州市科技计划项目科学研究专项(2016070100 46);广州医科大学博士启动项目(2014C06)

摘　　要：【目的】探讨鼻咽癌异常表达的SOD1及其对细胞迁移能力的影响和可能的分子机制。【方法】采用免疫组化技术检测癌和癌旁组织中SOD1的表达(n=10),采用脂质体转染si RNA下调SOD1表达,用抑制剂LCS-1抑制SOD1,划痕实验及迁移实验检测其对鼻咽癌细胞体外迁移能力的影响,定量PCR检测上皮细胞分子标志物E-cadherin及间质型分子Vimentin及转录因子Twist的m RNA水平,Western Blot法检测E-cadherin、Vimentin蛋白水平。【结果】与癌旁组织相比,7例癌组织中SOD1相对高表达(70%);在鼻咽癌细胞中,SOD1在高转移细胞系5-8F、S18及CNE2中较低转移细胞系6-10B中高表达。在5-8F、CNE2细胞中敲低或抑制SOD1后鼻咽癌细胞的迁移力下降,同时上皮型分子E-cadherin的m RNA和蛋白水平被上调、间质型分子Vimentin和转录因子Twist的表达下调。【结论】SOD1可能通过调控鼻咽癌细胞上皮间质转换(EMT)促进鼻咽癌细胞的迁移。【Objective】To explore the aberrant expression of SOD1 gene in nasopharyngeal carcinoma tissues and adjacent tissues,as well as in NPC cell lines,then to observe the effect of SOD1 on NPC cells metastatic ability and investigate the intrinsicmechanism.【Methods】Immunohistochemical technique was used to examine SOD1 expression in carcinoma tissues and adjacent tissues（n = 10）. Small interfering RNAs and inhibitor LCS-1 were used to knockdown of SOD1 expression and inhibit SOD1 activity,respectively. Then,wound healing test and migration assay were applied to detect cell metastatic ability in vitro. Real-time PCR and Western Blot were used to analyze the expression of EMT-related genes（E-cadherin,Vimentin,Twist）.【Results】SOD1 was found to be significantly up-regulated in nasopharyngeal carcinoma tissues（n = 7,70%）,compared to control. SOD1 was also highly expressed in highly metastatic potential NPC cell lines（CNE2,5-8F,S18）compared with low metastatic ability cell lines（6-10B）.Knockdown SOD1 expression or inhibit SOD1 activity suppress cell motility in CNE2 and 5-8F cells. Finally,we demonstrate that SOD1 inhibition plays a role in induction of epithelial marker E-cadherin and has an opposite effect on mesenchymal marker vimentin and transcriptional factor twist.【Conclusion】These results suggest that SOD1 contributes to EMT and might be important for tumor metastasis in NPC.

关 键 词：上皮间质转化 鼻咽癌 超氧化物歧化酶1 

分 类 号：R34[医药卫生—基础医学]