抑制SOD1调节上皮间质转化抑制鼻咽癌细胞迁移

摘要

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 intrinsic⁃mechanism.[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 vimen tin and transcriptional factor twist.[Conclusion]These results suggest that SOD1 contributes to EMT and might be important for tumor metastasis in NPC.%【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siRNA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mRNA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mRNA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。