格尔德霉素对宫颈癌HeLa细胞中bcl-2表达的影响Effects of geldanamycin on expression of bcl-2 in human cervical cancer cell line HeLa.
杜雪;糜若然;瞿全新;屈野;
摘要(Abstract)：
目的:观察格尔德霉素(geldanamycin,GA)在体外对宫颈癌HeLa细胞抗凋亡基因bcl-2和mRNA转录、蛋白表达水平的影响。方法:分别给予宫颈癌HeLa细胞0,0.02,0.2,2,10μmol/L浓度GA处理24h,用annexin V方法检测细胞凋亡,半定量PCR检测bcl-2、Hsp90 mRNA转录水平,用10μmol/L的GA处理HeLa细胞3、12、24、48h后,Western blot检测bcl-2、Hsp90蛋白表达水平的变化。结果:宫颈癌HeLa细胞经不同浓度的GA作用24h,细胞凋亡指数呈剂量依赖性增加,bcl-2 mRNA表达呈剂量依赖性降低,bcl-2蛋白表达水平呈时间依赖性降低,处理组与对照组之间的差异有统计学意义;但GA对Hsp90 mRNA和蛋白表达水平无明显影响。结论:GA可抑制宫颈癌HeLa细胞抗凋亡基因bcl-2的转录和表达,促进凋亡。
关键词(KeyWords)： 宫颈肿瘤;HeLa细胞;细胞系;格尔德霉素;基因,bcl-2;热休克蛋白90
基金项目(Foundation):
作者(Authors): 杜雪;糜若然;瞿全新;屈野;
DOI: 10.13283/j.cnki.xdfckjz.2008.04.022
参考文献(References)：
- [1]Cohen-Saidon C,Carmi I,Keren A,et al.Antiapoptoticfunction of bcl-2 in mast cells is dependent on its associ-ation with heat shock protein 90 beta[J]Blood,2006,107:1413-1420
- [2]Bishop SC,Burlison JA,Blagg BS.Hsp90:a novel targetfor the disruption of multiple signaling cascades[J].CurrCancer Drug Targets,2007,7:369-388
- [3]Schmitt E,Gehrmann M,Brunet M,et al.Intracellular andextracellular functions of heat shock proteins:repercus-sions in cancer therapy[J].J Leukoc Biol,2007,81:15-27
- [4]Powers MV,Workman P.Targeting of multiple signallingpathways by heat shock protein 90 molecular chaperoneinhibitors[J].Endocr Relat Cancer,2006,13:125-135
- [5]Gooljarsingh LT,Fernandes C,Yan K,et al.A biochemi-cal rationale for the anticancer effects of Hsp90 inhibi-tors:slow,tight binding inhibition by geldanamycin and itsanalogues[J].Proc Natl Acad Sci U S A,2006,103:7625-7630
- [6]Duus J,Bahar HI,Venkataraman G,et al.Analysis of ex-pression of heat shock protein-90(Hsp90)and the effectsof Hsp90 inhibitor(17-AAG)in multiple myeloma[J].Leuk Lymphoma,2006,47:1369-1378