地塞米松诱导结肠癌细胞凋亡的机制研究  

Mechanism of apoptosis of human colon carcinoma cells induced by dexamethasone in vitro

作　　者：周进明[1] 彭秋平[2] 周琪[2] 钟大平[2] 黄树涛[2] 施绍用[2] 梁后杰[2] 

机构地区：[1]解放军第521医院,137001 [2]第三军医大学西南医院肿瘤科,重庆400038

出　　处：《临床肿瘤学杂志》2009年第11期969-973,共5页Chinese Clinical Oncology

基　　金：国家自然科学基金资助项目(30171067)

摘　　要：目的:探讨地塞米松(Dex)体外抑制结肠癌细胞株的增殖并诱导其凋亡的作用机制。方法:采用MTT及流式细胞仪检测细胞增殖抑制及凋亡,RT-PCR检测GR、IκB及Bcl-2的表达改变,凝胶迁移或电泳迁移率实验(EMSA)检测Dex作用过程中的NF-κB活性改变。结果:Dex体外作用后,对4种结肠癌细胞株LoVo、HCT-116、HT-29及SW-480均有抑制作用,LoVo和HCT-116细胞作用最显著。流式细胞仪检测显示,Dex(1×10-4mol/L)诱导72 h后,在LoVo和HCT-116细胞检测到细胞凋亡和坏死峰,明显高于未加Dex的对照组,具有显著性差异。RT-PCR检测显示Dex作用后GRα、IκB表达升高,Bcl-2无明显改变,EMSA结果也显示NF-κB活性明显降低。结论:地塞米松可能通过上调GRα、IκB表达,抑制NF-κB活性来抑制LoVo细胞的增殖,并诱导其凋亡。Objective：To explore the mechanism of apoptosis induced by dexamethasone in human colon carcinoma cell lines in vitro.Methods：GR protein was determined by immunohistochemistry.Proliferation and apoptosis was detected by MTT and flow cytometer.The mRNA expression of GRα,IκB and Bcl-2 was examined by semi-quantitative RT-PCR.The activity of NF-κB was measured by EMSA.Results：The glucocorticoid receptor was determined in LoVo and HCT-116,not in HT-29 and SW-480.Dexamethasone had an inhibitory effect on four kinds of human colon cancer cell lines,respectively.LoVo and HCT-116 cells were more sensitive.Apoptosis and necrosis cusps were investigated by flow cytometer in LoVo and HCT-116,the rates of apoptosis and necrosis were higher than those in the control groups without dexamethasone.The supression of NF-κB activity,up-regulation of the mRNA expression of GRα and IκB occurred in LoVo cells 6,12 and 24 hours after dexamethasone treatment.The expression of Bcl-2 was not changed in LoVo cell.Conclusion：The mechanism of apoptosis and inhibition of proliferation induced by dexamethasone in human colon carcinoma cell may involve up-regulation of GRα and IκB and supression of NF-κB activity.

关 键 词：结肠癌 糖皮质激素受体 细胞凋亡 地塞米松 

分 类 号：R735.3[医药卫生—肿瘤]