HBXIP抑制补体介导的细胞毒活性促进肝癌免疫逃逸的机制研究  

Mechanism study of HBXIP promoting immune escape of liver cancer cells by inhibiting complement-mediated cytotoxic activity

作　　者：安萍[1] 沈学斌 卞丽[1] 尚宁[1] 郭佳晶 石晓琳 贾景飞 AN Ping;SHEN Xue-Bin;BIAN Li;SHANG Ning;GUO Jia-Jing;SHI Xiao-Lin;JIA Jing-Fei(Department of Hepatology and Immunology,the Sixth People′s Hospital of Shenyang,Shenyang 110006,China)

机构地区：[1]沈阳市第六人民医院肝病免疫科,沈阳110006 [2]辽阳市传染病院肝病科,辽阳111000

出　　处：《中国免疫学杂志》2020年第14期1680-1683,共4页Chinese Journal of Immunology

基　　金：辽宁省科学技术计划项目(2013020199-225)资助。

摘　　要：目的:探讨乙肝病毒X蛋白结合蛋白(HBXIP)对补体介导的细胞毒活性的影响及其在肝癌细胞免疫逃逸中的作用。方法:构建NC-shRNA和HBXIP-shRNA慢病毒稳定细胞系,台盼蓝染色检测HBXIP对补体介导的细胞毒作用的影响;Western blot检测HBXIP对CD46、CD55和CD59表达的影响;免疫荧光检测HBXIP对NF-κB活性的影响;HBXIP-shRNA细胞中过表达NF-κB,Western blot检测CD46、CD55和CD59表达变化。结果:HBXIP-shRNA细胞补体介导的细胞毒作用显著高于NC-shRNA细胞(P<0.05)。与NC-shRNA细胞相比,HBXIP-shRNA细胞CD46、CD55、CD59表达显著下降,NF-κB活性明显降低(P<0.05)。HBXIP-shRNA细胞中过表达NF-κB,CD46、CD55和CD59蛋白表达水平明显回升(P<0.05)。结论:HBXIP可能通过介导NF-κB活性调节CD46、CD55、CD59表达参与肝癌细胞免疫逃逸,为肝癌临床治疗提供新靶点。Objective:To investigate effect of Hepatitis B X-interacting protein(HBXIP)on complement-mediated cytotoxic activity and its role in immune escape of liver cancer cells.Methods:NC-shRNA and HBXIP-shRNA lentiviral stable cell lines were constructed,and effect of HBXIP on complement-mediated cytotoxicity was detected by trypan blue staining.Western blot was used to analyze effect of HBXIP on expression of CD46,CD55 and CD59.Effect of HBXIP on NF-κB activity was analyzed by immunofluore scence.NF-κB was overexpressed in HBXIP-shRNA cells,and change in expressions of CD46,CD55 and CD59 were examined by Western blot.Results:Complement-mediated cytotoxicity of HBXIP-shRNA cells was significantly higher than that of NC-shRNA cells(P<0.05).Compared with NC-shRNA cells,expressions of CD46,CD55 and CD59 in HBXIP-shRNA cells were significantly decreased,and activity of NF-κB was also significantly decreased(P<0.05).After overexpression of NF-κB in HBXIP-shRNA cells,expression levels of CD46,CD55 and CD59 were significantly increased(P<0.05).Conclusion:HBXIP may regulate expressions of CD46,CD55 and CD59 by mediating activity of NF-κB,and paticipate in immune escape of liver cancer cells which may provide new target for clinical treatment of liver cancer.

关 键 词：HBXIP 肝癌 免疫逃逸 NF-ΚB 膜结合补体调节蛋白 

分 类 号：R392[医药卫生—免疫学]