榄香烯阻碍大鼠胶质瘤C6细胞ERK信号通路中Hsp90/Raf-1分子复合体的形成  

Inhibition of elemene on Hsp90/Raf-1 molecular complex in C6 glioblastoma cells

作　　者：赵永顺[1] 董斌[2] 吴春明[2] 位振清[2] 徐英辉[2] 

机构地区：[1]大连医科大学,大连116044 [2]大连医科大学附属第一医院神经外科,大连116011

出　　处：《实用药物与临床》2011年第4期274-276,共3页Practical Pharmacy and Clinical Remedies

摘　　要：目的探讨莪术提取物榄香烯抑制胶质瘤细胞体外增殖的机制。方法采用细胞计数、免疫共沉淀、Western印迹等方法,分别检测不同浓度、不同作用时间榄香烯对C6胶质瘤细胞的增殖影响、对C6细胞中与Raf-1结合形成分子复合体的Hsp90水平的影响、对C6细胞Hsp90、Raf-1、ERK蛋白质表达的影响。结果榄香烯对大鼠C6胶质瘤细胞具有明显的抑制增殖作用,该增殖抑制效应呈剂量、时间依赖性。榄香烯可明显下调C6细胞中与Raf-1结合的Hsp90水平及C6细胞的磷酸化Raf-1、ERK表达,但不影响总Hsp90的表达水平。结论榄香烯能有效抑制胶质瘤细胞的体外增殖,破坏Hsp90的分子伴侣功能,阻碍Hsp90/Raf-1复合体的形成,使Raf-1不能被活化,最终下调胶质瘤细胞赖以生存的Raf/MEK/ERK通路,这可能是榄香烯抑制C6细胞增殖的机制。Objective To study the inhibition mechanism of elemene on proliferation of rat C6 glioblastoma cells in vitro.Methods Effect of elemene on the proliferation of C6 glioblastoma cells,the level of Hsp90 combined to Raf-1 and expression of Hsp90,Raf-1 and ERK protein were tested by cell-counting,co-immunoprecipitation assay and Western blotting analysis at different concentrations or time points,respectively.Results The proliferation of C6 glioblastoma cells was inhibited by elemene in a dose/time-dependent manner.The level of Hsp90 combined to Raf-1 and the expression of phosphorylated Raf-1 and ERK were down-regulated,but the level of total Hsp90 in C6 cells had no change.Conclusion Elemene can inhibit the proliferation of C6 glioblastoma cells in vitro,disrupt the molecular chaperone function of Hsp90,decrease the recruitment of Hsp90 in the Hsp90/Raf-1 complex,block the activation of Raf-1,lead to down-regulation of ERK pathway,and these may be the mechanism of anti-proliferation effect of elemene.

关 键 词：榄香烯 胶质瘤 HSP90 RAF-1 ERK 

分 类 号：R739.41[医药卫生—肿瘤]