转录因子Foxp3在肝癌细胞中的表达及意义  

Expression and significiance of Foxp3 in hepatocellular carcinoma

作　　者：王莉[1] 梅铭惠[1] 孙煦化[1] 陈红松[2] 张恒辉[2] 费然[2] 谢兴旺[2] 

机构地区：[1]桂林医学院附属医院,广西桂林541004 [2]北京大学肝病研究所

出　　处：《山东医药》2010年第48期8-11,共4页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(30772499);广西研究生教育创新计划资助(KY2009036)

摘　　要：目的研究转录因子Foxp3在肝癌细胞中的表达及其对肿瘤免疫微环境的作用。方法用常规RT-PCR和基因表达谱芯片检测Foxp3在10种肝癌细胞系中的表达,进一步用Western blot、免疫组化和流式细胞术验证其蛋白水平的表达;将表达Foxp3的肿瘤细胞及用Foxp3 shRNA沉默后的肿瘤细胞分别与CD4+CD2-5T细胞共培养,CFSE评价免疫效应细胞增殖情况。结果 Foxp3在所有的肝癌细胞系中均出现表达;肝癌细胞与CD4+T细胞进行共培养,可显著抑制共培养体系中CD+4T细胞增殖及其表面标记的表达;肝癌细胞Foxp3表达沉默后,可显著逆转共培养体系中肝癌细胞对CD4+T细胞增殖的表达抑制。结论在肝细胞癌(HCC)细胞系及部分HCC患者组织中均发现Foxp3的表达,肝癌细胞Foxp3的表达参与对肿瘤微环境中效应性T细胞增殖的抑制。Objective To investigate the expression of forkhead transcription Foxp3 in hepatocarcinoma cell lines and to explore its significance in tumor immune micro-environment.Methods Conventional RT-PCR technique and cDNA expression profile were used to detect the expression of Foxp3 mRNA in 10 hepatocarcinoma cell lines.Protein expression was assessed by using Western blot,immunocytochemistry and flow cytometry methods.Down-regulation of Foxp3 was used by Foxp3 shRNA in hepatocellular carcinoma（HCC） cells.The immune-related inhibitory functions in Foxp3-expressing HCC cells were evaluated by co-culturing tumor cells with native CD＋4T cells.Results Foxp3 mRNA and protein were detected in all HCC cell lines.The hepatoma cells could significantly inhibit of CD＋4T cell proliferation in the co-culture system.There could be a significant reversal of CD＋4T cell proliferation and the expression of surface marker after silencing the expression of Foxp3 by shRNA in hepatoma cells and decrease the expression of Foxp3 in CD＋4T cells.The Foxp3-expressing HCC cells could inhibit the CD＋4effector T cells proliferation.Conclusion Foxp3 expressed in all HCC cells and it might be involved in tumor cell mediated immune-suppression.

关 键 词：肝肿瘤 FOXP3 肿瘤免疫微环境 

分 类 号：R730.7[医药卫生—肿瘤]