NDRG2在热疗抗肝癌细胞作用中的影响  

The effect of NDRG2 on hyperthermia retards hepatocellular carcainoma cells

作　　者：郭燕[1] 刘文超[1] 马骥[1] 王倩荣[1] 张媛[1] 

机构地区：[1]第四军医大学西京医院肿瘤科,陕西西安710032

出　　处：《现代肿瘤医学》2014年第2期259-264,共6页Journal of Modern Oncology

基　　金：国家自然科学基金资助项目(编号:30973437)

摘　　要：目的:探讨NDRG2对热疗诱发的热应激抗肝癌细胞作用的影响。方法:分别给予肝癌HepG-2和Huh-7细胞37℃、39℃、41℃、43℃、45℃水浴30min的热刺激后,采用细胞划痕、Transwell和Western blot方法对各组细胞的迁移、侵袭能力和NDRG2、MMP-2/9蛋白表达量进行检测,同时应用流式细胞技术检测肿瘤细胞的坏死和凋亡情况。结果:与37℃(对照组)相比,45℃组HepG2和Huh-7细胞的迁移和侵袭能力均有显著降低(P<0.05),细胞内MMP-2及MMP-9分泌量明显下降,同时伴随NDRG2表达量明显上升。通过比对NDRG2联合热作用对肝癌细胞的治疗效果,发现在正常表达NDRG2的对照组细胞(CherryHepG-2)的凋亡率会随着加热温度的增加而增加,同时坏死率显著增高(P<0.05)。然而,给予NDRG2过表达组细胞(NDRG2-HepG2)43℃热处理后,细胞凋亡率和抗细胞侵袭能力可高达45℃热作用于对照组细胞的水平,而细胞坏死率却没有增加。结论:45℃的热应激可明显抑制肝癌细胞的迁移和侵袭能力;NDRG2联合热作用可对肝癌细胞产生较好的促凋亡和抗侵袭效果。Objective：To investigate the effect of NDRG2 on hyperthermia retards hepatocellular carcainoma cells.Methods：Both HepG-2 and Huh-7 cells were subjected to water bath at different temperatures （37℃,39℃,41℃,43℃ and 45℃）for 30 min.The anti-migration,anti-invasive effect,expression of NDRG2,MMP-2/MMP-9 and type of cell death were detected with cell wound healing assay,Transwell assay,Western blot and flow cytometry,respectively.Results：Compared with control group （37℃）,heat treated at 45℃ significantly reduced the percentage invaded cells and the expression of MMP-2 and MMP-9 in HepG-2 and Huh-7 cells.Meanwhile,the expression of NDRG2 was increased by heat stress at 45℃ in （P〈0.05）.We examined the therapeutic effect of NDRG2 combined with HT against HCC.HepG-2 cells treated at 45℃ showed significantly higher rate of cell apoptosis,compared with those treated at 43℃.HT at 45℃ caused massive increase in number of necrotic cells in comparison with cells treated at 43℃.Moveover,combination of NDRG2 and HT at 43℃ resulted in increased level of apoptosis and anti-invasive effect and reduced necrosis,compared with treatment of HT at 45℃.Conclusion：HT at 45℃ could inhibit migration and invasion of HCC cells.NDRG2 synergizes with HT to inhibit invasiveness of HCC cells and decrease spontaneous necrosis.

关 键 词：热应激 NDRG2 肝癌 

分 类 号：R730.2[医药卫生—肿瘤] R735.7[医药卫生—临床医学]