HIF-1α/IL-8/NF-κB轴介导缺氧诱导肝癌细胞迁移、侵袭的实验研究  

HIF-1α/IL-8/NF-κB axis mediate hypoxia induced migration and invasion of hepatocellular carcinoma

作　　者：吴思 艾芬[1] 朱聚[1] 肖朝文[2] 吕波 WU Si;AI Fen;ZHU Ju;XIAO Chaowen;LV Bo(Department of Emergency,Wuhan Central Hospital,Tongji Medical College,Huazhong University of Science and Technology,Hubei 430014,China)

机构地区：[1]华中科技大学同济医学院附属武汉中心医院急诊科,武汉430014 [2]华中科技大学同济医学院附属武汉中心医院肝胆外科,430014

出　　处：《临床肿瘤学杂志》2018年第9期780-784,共5页Chinese Clinical Oncology

摘　　要：目的探讨HIF-1α在缺氧条件下诱导肝癌细胞迁移和侵袭作用及可能的分子机制。方法缺氧和正常培养条件下培养人正常肝细胞系WRL68、人肝癌细胞系Hep G2和SMMC7721,实时荧光定量PCR(QPCR)和Western blotting检测HIF-1αm RNA和蛋白的表达; Hep G2细胞分别转染NC无义核酸序列(NC组)、si HIF-1α(HIF-1α组)和si IL-8(IL-8组),Western blotting检测HIF-1α、IL-8和NF-κB蛋白表达;缺氧条件下干扰HIF-1α和IL-8并检测Hep G2的迁移和侵袭能力的改变。结果缺氧条件下,Hep G2和SMMC7721细胞系中的HIF-1αm RNA和蛋白水平显著高于人正常肝细胞系。与空白对照组的0. 98±0. 104和NC组的0. 92±0. 032比较,HIF-1α组HIF-1α蛋白表达量显著下降为0. 39±0. 077,差异有统计学意义(P<0. 05);缺氧条件下HIF-1α组IL-8蛋白表达量为0. 31±0. 043,显著低于空白对照组的0. 96±0. 114和NC组的0. 90±0. 081,差异有统计学意义(P<0. 05)。缺氧条件下NC组Hep G2迁移、侵袭细胞数分别为91. 2±8. 2和121. 1±6. 7,显著高于HIF-1α组的36. 3±5. 9和47. 7±3. 3,差异有统计学意义(P<0. 05);亦显著高于IL-8组的49. 4±5. 6和39. 6±5. 1,差异有统计学意义(P<0. 05)。结论 HIF-1α通过调控IL-8表达促进缺氧诱导的肝癌细胞迁移和侵袭。Objective To investigate the effect and molecular mechanism of HIF-1α on migration and invasion of hepatocellular carcinoma（HCC） cells induced by hypoxia.Methods Human normal hepatocyte line WRL68, HCC cell line HepG2 and SMMC7721 were cultured under hypoxia and normal culture conditions. Real time quantitative PCR （QPCR） and Western blotting were used to detect the expression of HIF-1α mRNA and protein. HepG2 cells were transfected with NC nonsense nucleic acid sequence （NC group）, siHIF-1α（HIF-1α group） and siIL-8 （IL-8 group）, respectively. Western blotting was used to detect the expression of HIF-1α, IL-8 and NF-κB protein. The changes of migration and invasion ability of HepG2 were detected by interfering with HIF-1α and IL-8.Results Under hypoxia, the levels of HIF-1α mRNA and protein in HepG2 and SMMC7721 cell lines were significantly higher than those in normal human hepatocytes. Compared with the control group and NC group, the expression of HIF-1 alpha protein in HIF-1 alpha group decreased significantly to 0.39±0.077 （ P 〈0.05）. Under hypoxia, the expression of IL-8 protein in HIF-1α group was 0.31±0.043,significantly lower than that in blank control group and NC group, and the difference was statistically significant （ P 〈0.05）. The number of HepG2 migrating and invading cells in NC group were 91.2±8.2 and 121.1±6.7 respectively, which were significantly higher than those in HIF-1α group （36.3±5.9 and 47.7±3.3）,and the difference was statistically significant （ P 〈0.05）;which were significantly higher than those in IL-8 group （49.4±5.6 and 39.6±5.1）,and the difference was statistically significant （ P 〈0.05）.Conclusion HIF-1α promotes the migration and invasion of hypoxia induced hepatocellular carcinoma cells through regulating IL-8 expression.

关 键 词：肝细胞癌 HIF-1Α IL-8 迁移 侵袭 

分 类 号：R735.7[医药卫生—肿瘤]