低氧环境地高辛通过抑制HIF-1α下调结肠癌HCT 116细胞VEGF表达的实验研究  

Digoxin inhibits expression of VEGF through HIF-1α under hypoxic condition in HCT116 Cells

作　　者：尹鹏[1] 胡君[1] 霍中华[1] 储著凌[1] 侯乐伟[1] 吕盛[1] 栾荣刚[1] 胡国强[1] 

机构地区：[1]解放军第四五四医院普外烧伤整形科,江苏南京210002

出　　处：《西部医学》2015年第3期335-337,343,共4页Medical Journal of West China

基　　金：南京军区科研课题(12mb020)

摘　　要：目的研究低氧环境下地高辛能否通过抑制HIF-1α下调结肠癌HCT 116细胞VEGF的表达。方法将HCT 116细胞分为常氧组(Normoxia组)、低氧组(Hypoxia组)和低氧+地高辛组(Hypoxia+Digoxin组)。在低氧环境下对结肠癌HCT 116细胞使用地高辛干预,在3个不同时间点(0、24和72h)使用MTT法对HCT 116细胞活性进行检测;同时在干预24小时后分别采用RT-PCR法和western blotting法对HCT 116细胞VEGF和HIF-1α的mRNA和蛋白水平进行检测。结果低氧环境下HCT 116细胞活性呈时间依赖性下降,差异均有统计学意义(均P<0.05);且在各时间点低氧+地高辛组细胞活性较低氧组细胞下降更加明显,差异均有统计学意义(均P<0.05)。在干预24小时后,HCT 116细胞VEGF和HIF-1αmRNA和蛋白的表达水平较未干预细胞明显降低(均P<0.05)。结论在低氧环境下,地高辛可以通过抑制HIF-1α的合成下调结肠癌HCT 116细胞VEGF的表达,抑制肿瘤细胞增殖。Objective To investigate the effect of digoxin on the expression of VEGF in colon cancer HCT116 cells in hypoxia.Methods Colon cancer HCT116 cells were divided into Normoxia group,Hypoxia group and Hypoxia＋Digoxin group.At specified time points（0,24 and 72h）,cell viabilities were detected by MTT assay.After 24 hours interventions,VEGF and HIF-1α mRNA were measured by RT-PCR,and VEGF and HIF-1α protein were analyzed by western blotting.Results The proliferation of HCT116 cells under hypoxic conditions was time-dependently suppressed by digoxin.Our data showed that hypoxia-induced overexpression of VEGF and HIF-1α both at the mRNA and protein levels.Meanwhile,the hypoxia-induced overexpression of VEGF and HIF-1α was inhibited by digoxin.Conclusion Digoxin reduces the expression of VEGF properly via the down-regulation of HIF-1α under hypoxic conditions in colon cancer HCT116 cells.

关 键 词：地高辛 HCT 116细胞 缺氧诱导因子-1α 血管生成因子 

分 类 号：R735.35[医药卫生—肿瘤]