Survivin通过Wnt/β-catenin信号通路调控食管癌的侵袭和迁移的机制研究

The Mechanism Research of Survivin Regulating Migration and Invasion in Esophageal Cancer via Wnt/β-catenin Signaling Pathway

目的:探讨Survivin在食管癌中的表达及对食管癌细胞中Wnt/β-catenin信号通路、侵袭和迁移的影响。方法:检测人食管癌组织和EC109细胞中Survivin蛋白的表达,并分析其与临床病例特征的相关性。脂质体介导法将Survivin小干扰RNA转染食管癌EC109细胞。基因mRNA相对表达量应用RT-qPCR检测。蛋白的表达应用免疫蛋白印迹(Western blot)检测。细胞存活率、迁移和侵袭能力应用MTT、划痕愈合和Transwell小室实验检测。结果:食管癌组织和EC109细胞中Survivin表达增高。食管癌组织的TNM分期、分化程度和淋巴结转移与Survivin阳性表达相关;RNA干扰下调Survivin后可显著抑制食管癌细胞内Survivin mRNA和蛋白的表达。下调Survivin后,食管癌细胞内wnt3α、β-catenin、cyclinD1和c-myc表达量下降,Wnt/β-catenin信号通路受到抑制,且食管癌细胞的存活、迁移和侵袭能力受到抑制。结论:下调Survivin基因可以通过影响Wnt/β-catenin信号通路而抑制食管癌细胞的存活、迁移和侵袭能力。

Objective:To investigate the expression of Survivin in esophageal cancer and its effect on Wnt/β-catenin signaling pathway,invasion and migration in esophageal cancer cells.Methods:The expression of Survivin protein in human esophageal cancer tissues and EC109 cells was examined and its correlation with clinical case characteristics was analyzed.Survivin small interfering RNA was transfected into oesophageal cancer EC109 cells by liposome mediated method.Relative expression of gene mRNA was detected by RT-qPCR.Protein expression was detected by immunoprotein blotting(Western blot).Cell viability,migration and invasion ability were measured by MTT,scratch healing and Transwell assays.Results:The expression of Survivin was increased in esophageal cancer tissues and EC109 cells.The TNM stage,differentiation and lymph node metastasis of esophageal cancer tissues correlated with positive Survivin expression;down-regulation of Survivin by RNA interference significantly inhibited Survivin mRNA and protein expression in esophageal cancer cells.The expression of wnt3α,β-catenin,cyclinD1 and c-myc in esophageal cancer cells decreased after down-regulation of Survivin,and the Wnt/β-catenin signaling pathway was inhibited,and the survival,migration and invasion ability of esophageal cancer cells were suppressed.Conclusion:Down-regulation of Survivin gene can inhibit the survival,migration and invasion of esophageal cancer cells by affecting the Wnt/β-catenin signaling pathway.