糖皮质激素受体阻断对雄激素非依赖性前列腺癌细胞的抑制作用

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1、万方数据主堡耋生垦堂苤查；!!!生!旦笙ii鲞箜i塑堡!i!』鱼鱼!!!!坚!望!!!!!!y!!：；!!堕!：!糖皮质激素受体阻断对雄激素非依赖性前列腺癌细胞的抑制作用闫天中武小强257·基础研究·【摘要】目的探讨糖皮质激素受体(GR)信号通路及下游炎症因子白细胞介素(IL一6)等在前列腺癌雄激素非依赖生长中的作用。方法体外培养人雄激素依赖性前列腺癌(ADPC)细胞株LNCaP和雄激素非依赖性前列腺癌(AIPC)细胞株DUl45，免疫细胞化学检测雄激素受体(AR)、GR、热休克蛋白(HSP90)和IL-6表达的差异，观察GR阻断剂RU486对LNCaP和DUl45生长的

2、影响，GR阻断后DUl45细胞HSP90、IL一6mRNA及蛋白表达的变化。结果LNCaP细胞AR+，GR，而DUl45细胞GR+，AR，DUl45细胞HSP90、IL_6表达明显强于LNCaP细胞(P<0．01)；RU486对LNCaP细胞生长的影响很小，而对DUl45细胞呈现出明显的浓度和时间依赖性抑制作用；RU486作用后DUl45细胞中HSP90、IL一6tuRNA及蛋白的表达明显降低。结论GR信号通路是DUl45细胞的主要成活途径，GR信号通路的异常活化并促进炎症因子HSP90、IL一6等的高表达是前列腺癌雄激素非依赖进展的重要原因。【关键词】前列腺癌；受体，糖

3、皮质激素；热休克蛋白；白细胞介素6；雄激素Inhibitoryefficacyofglucocorticoidreceptorblockingonandrogen-independentprostatecancercellsYanTianzhong，WMXiaoqiang．DepartmentofUrology，HenanProvincialPeople’SHospital，Zhengzhou450003，ChinaCorrespondingauthor：YanTianzhong，Email：ytz460@hotmail．com[Abstract]0bjectiveTos

4、tudytheeffectsofglucocorticoidreceptor(GR)signalpathwayanddownstreamcytokinesonandrogen—independentgrowthofprostatecancer(PC)cells．MethodsThehumanandrogen-dependentPC(ADPC)celllineLNCaPandandrogen-independentPC(AIPC)celllineDUl45wereculturedinvitro．Immunocytochemistrywasusedtoexaminetheex

5、pressionsoftheandrogenreceptor(AR)，GR，HSP90andinterleukin-6(IL一6)．TheGRantagonistRU486wasusedtotreatculturedcells，andtheeffectsofRU486ontheproliferationofbothcelllineswereanalyzedbyMTTassay．ExpressionsofHSP90andILr6mRNAandproteinwereassessedbvRT—PCRandWesternblottingrespectively．ResultsLN

6、CaPcellswereAR—positiveandGR—negative，whereasDUl45cellswereGR—positiveandAR—negative．TheexpressionsofHSP90andIL-6weresignificantlystrongerinDUl45cellsthaniDLNCaPcells(P<0．01)．RU486hadnoobviouslyeffectsonthegrowthofLNCaPcells，butexertedasignificanttime-anddose-dependentgrowthinhibitiononDU

7、l45cells．RU486treatmentinDUl45cellsalsoresultedinadose-dependentdecreaseintheexpressionsofHSP90andIL-6mRNAandprotein．ConclusionsGRsignalpathwaymaybethemainsurvivalpathwayforDUl45cells．AbnormalhyperactivationofGRsignalpathwayanditspromotingtheexpressionsofHSP90andIL一