吉林大学学报(医学版)

• 基础研究 • 上一篇    下一篇

肝星状细胞经趋化因子SDF-1/CXCR4轴途径促进肝癌细胞侵袭的作用及其机制

李四光1,刘凯歌2,常远鸿3   

  1. 1.西安医学院临床医学院外科教研室,陕西 西安 710021;2.西安医学院附属医院消化内科,陕西  西安 710077;3.陕西省西安市第四医院消化内科,陕西 西安710004
  • 收稿日期:2012-09-04 出版日期:2013-07-28 发布日期:2013-08-17
  • 通讯作者: 李四光(Tel:029-86177630, E-mail: lsg0916@sina.com) E-mail:lsg0916@sina.com
  • 作者简介:李四光(1974-)男,山西省晋城市人,讲师,医学硕士,主要从事消化系统肿瘤的研究。
  • 基金资助:

    陕西省教育厅专项科研计划项目资助课题(11JK 0704)

Effect of hepatic stellate cell through chemotatic factor SDF-1/CXCR4 axis on promoting hepatocellular carcinoma invasion and its mechanism

LI Si-guang1,LIU Kai-ge2,CHANG Yuan-hong3   

  1. 1.Teaching and Research Section of Surgery,College of Clinical Medicine,Xi’an Medical University,Xi’an 710021,China; 2.Department of Gastroenterology,Affiliated Hospital,Xi’an Medical University,Xi’an 710077,China; 3.Department of Gastroenterology, Fourth Hospital of Xi’an City,Shaanxi Province,Xi’an 710004,China
  • Received:2012-09-04 Online:2013-07-28 Published:2013-08-17

摘要:

目的:探讨肝星状细胞(HSC)通过SDF-1/CXCR4轴对肝癌细胞侵袭的影响和可能机制,为研究肝癌的侵袭过程提供依据。方法: 采用Western blotting和RT-PCR检测HSC LX02和肝癌细胞MHCC97、SMMC7721、Hep3B、HepG2中SDF-1和CXCR4的表达。采用Transwell实验检测LX02共培养或外源性SDF-1干预对肝癌细胞HepG2以及CXCR4基因沉默后的HepG2侵袭的影响。Western blotting法检测上皮标志E-Cadherin和间质标志Vimentin的表达水平。结果:与肝癌细胞比较,LX02中趋化因子SDF-1呈高表达(P<0.05)。4株人肝细胞癌细胞均有CXCR4高表达。HSC或SDF-1均能促进肝癌细胞HepG2侵袭(P<0.05),并诱导E-Cadeherin蛋白表达下调,Vimentin蛋白表达上调。通过RNA干扰技术靶向沉默肝癌细胞CXCR4基因后,HSC和SDF-1对肝癌细胞HepG2侵袭能力均无明显影响(P>0.05),肝癌细胞E-Cadeherin、Vimentin蛋白及mRNA表达水平亦无明显变化。结论:HSC可通过SDF-1/CXCR4轴促进肝癌细胞侵袭,其机制可能与诱导肝癌细胞上皮-间质转化有关。

关键词: 肝肿瘤, 侵袭, 基质细胞衍生因子1, CXCR4, 肝星状细胞

Abstract:

Abstract:Objective To explore the impact of hepatic stellate cell (HSC)in hepatocellular carcinoma invasion through SDF-1/CXCR4 axis and its mechanism,and to provide basis for research on hepatocellular carcinoma  invasion. Methods The expressions of SDF-1 and CXCR4 in HSC LX02,hepatocellular carcinoma cells(MHCC97,SMMC7721,Hep3B,and HepG2) were examined by Western blotting  method  and RT-PCR method. In addition,Transwell invasion assay was carried out to analyze the influence of HSC LX02 and SDF-1 on invasion of hepatocellular carcinoma cells HepG2 under normal condition or CXCR4 gene silence condition. Then Western blotting method was performed to evaluate the expressions of epithelial marker E-Cadherin protein and mesenchymal marker Vimentin protein. Results Compared with hepatocellular carcinoma cells,SDF-1 was over-expressed in HSC LX02 (P<0.05).CXCR4 highly expressed  in all hepatocellular carcinoma cells. Co-culture with HSC LX02 or treatment with SDF-1 both increased the invasion of hepatocellular carcinoma cells HepG2 (P<0.05),and decreased E-Cadeherin protein expression (P<0.05) and increased Vimentin protein expression (P<0.05). Furthermore,after silence of CXCR4 gene by RNA jamming technique in HepG2 cells,neither co-culture with HSC LX02 nor treatment with SDF-1 had impact in invasion of hepatocellular carcinoma cells(P>0.05),and there were no changes in the E-Cadeherin (P>0.05) and Vimentin (P>0.05) protein expression levels. Conclusion HSC can promote hepatocellular carcinoma cells invasion through chemokine SDF-1/CXCR4 axis,and the mechanism may be realted to epithelial-mesenchymal transition of carcinoma cells.

Key words: hepatocellular carcinoma, invasion, stromal cell derived factor-1, CXCR4, stellate cell

中图分类号: 

  • R735.7