肝癌细胞异位过表达IL-12的抗肿瘤作用研究  

Anti-tumor effect of ectopic-expression of IL-12 in hepatocellular carcinoma cells

作　　者：穆永亮 赵华俊 张建[1] 韩秋菊[1] MU Yong-Liang;ZHAO Hua-Jun;ZHANG Jian;HAN Qiu-Ju(Institute of Immunopharmaceutical Sciences,School of Pharmaceutical Sciences,Shandong University,Jinan 250012,China)

机构地区：[1]山东大学药学院免疫药物学研究所

出　　处：《中国免疫学杂志》2019年第23期2864-2868,共5页Chinese Journal of Immunology

基　　金：山东省重点研发项目(2017GSF18159);山东省自然基金(ZR2017BH029);山东大学基本科研业务项目(2017JC004)资助

摘　　要：目的:探讨肝癌细胞异位过表达IL-12的抗肝细胞癌作用。方法:构建鼠源IL-12真核表达载体并转染肝癌细胞系。体外实验中利用CCK-8法检测细胞增殖水平,Transwell法检测细胞侵袭能力,FACS检测PD-L1表达以及免疫细胞活化水平,Western blot检测STAT1信号通路的活化;建立小鼠移植肿瘤模型,瘤内注射IL-12载体,测定肿瘤体积并利用FACS检测免疫细胞活化。结果:肝癌细胞异位过表达IL-12能够抑制Hepa1-6细胞增殖、侵袭以及荷瘤小鼠肿瘤生长,并进一步增强CD8+T细胞活化水平。结论:异位过表达IL-12不仅能够直接抑制肝癌细胞生长,还能通过活化免疫细胞增强其抗肿瘤作用。Objective:To investigate the anti-tumor effect of ectopic expression of IL-12 on hepatocellular carcinoma(HCC)cells.Methods:The murine IL-12 expression vector was constructed and transfected into HCC cells.CCK8 method was used to detect cell proliferation;Transwell assay was used to evaluate cell invasion,and flow cytometry was used to analyze the expression of PD-L1 and activation of immune cells.Furthermore,Western blot was used to detect the activation of STAT1 signal pathway.Then,tumor volume was measured and the activation of immune cells were detected by FACS after intratumoral injection of IL-12 into mice bearing Hepa1-6 cells.Results:Ectopic expression of IL-12 in HCC could inhibit the proliferation and invasion of Hepa1-6 cells,intratumoral injection of IL-12 also inhibited tumor growth in vivo.Furthermore,over-expression of IL-12 in HCC promoted the activation and cytotoxicity of CD8+T cells in vitro and in vivo.Conclusion:Ectopic overexpression of IL-12 can not only directly inhibit the growth of HCC,but also activate the immune cells and exert their anti-tumor effect.

关 键 词：IL-12 肝癌 T细胞 肿瘤微环境 

分 类 号：R392.1[医药卫生—免疫学]