全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...
药学学报  2015 

雷公藤内酯醇对人lncap细胞雄激素受体表达的调控及其机制

, PP. 1246-1251

Keywords: 雷公藤内酯醇,前列腺癌,雄激素受体,pi3k/akt/nf-κb通路

Full-Text   Cite this paper   Add to My Lib

Abstract:

本文研究了雷公藤内酯醇(triptolide,tp)对人前列腺癌lncap细胞内雄激素受体(androgenreceptor,ar)表达影响的作用机制。采用实时定量pcr和westernblot方法检测tp处理后lncap细胞中ar的mrna和蛋白表达的变化,以及使用tp和nf-κb抑制剂共处理后lncap细胞ar蛋白表达的变化;采用rf克隆法构建系列pgl3-ar启动子报告基因载体并转染至lncap细胞,检测tp对lncap细胞ar转录的调节作用;采用westernblot检测可能起调节作用的上游蛋白。结果表明,tp处理lncap细胞48h后,lncap细胞ar的mrna和蛋白的表达随着药物浓度增加而下降,同时ar靶基因part1及前列腺特异性抗原(prostatespecificantigen,psa)的表达也受到抑制;成功构建系列pgl3-ar启动子报告基因载体,测序结果表明,插入的目的序列正确且无碱基突变,转染lncap细胞后双荧光素酶报告基因检测系统证实其具有启动子活性;启动子报告基因实验结果表明,tp在转录水平下调ar的表达;与ar启动子活性相关的pi3k/akt/nf-κb通路蛋白表达下调。说明tp可能通过pi3k/akt/nf-κb通路下调人前列腺癌lncap细胞ar的转录活性。

References

[1]  siegelr,maj,zouz,etal.cancerstatistics,2014[j].cacancerjclin,2014,64:9-29.
[2]  bixg,hanrq,zhoujy,etal.ananalysisonincidenceandmortalityofprostatecancerinchina,2009[j].chinacancer(中国肿瘤),2013,22:417-422.
[3]  fidlerjm,lik,chungc,etal.pg490-88,aderivativeoftriptolide,causestumorregressionandsensitizestumorstochemotherapy[j].molcancerther,2003,2:855-862.
[4]  liuq.triptolideanditsexpandingmultiplepharmacologicalfunctions[j].intimmunopharmacol,2011,11:377-383.
[5]  huangw,het,chaic,etal.triptolideinhibitstheproliferationofprostatecancercellanddownregulatessumo-specificprotease1expression[j].plosone,2012,7:e37693.
[6]  koochekpours.androgenreceptorsignalingandmutationsinprostatecancer[j].asianjandrol,2010,12:639-657.
[7]  sharifin.mechanismsofandrogenreceptoractivationincastration-resistantprostatecancer[j].endocrinology,2013,154:4010-4017.
[8]  tilkid,evanscp.thechanginglandscapeofadvancedandcastrationresistantprostatecancer:latestscienceandreviseddefinitions[j].canadianjurol,2014,21:7-13.
[9]  el-ammj,pateln,freemana,etal.metastaticcastration-resistantprostatecancer:criticalreviewofenzalutamide[j].clinmedinsightsoncol,2013,7:235-245.
[10]  mitchellt,ramos-montoyaa,diantoniom,etal.downregulationofandrogenreceptortranscriptionbypromoterg-quadruplexstabilizationasapotentialalternativetreatmentforcastrate-resistantprostatecancer[j].biochemistry,2013,52:1429-1436.
[11]  linb,whitejt,fergusonc,etal.part-1:anovelhumanprostate-specific,androgen-regulatedgenethatmapstochromosome5q12[j].cancerres,2000,60:858-863.
[12]  vandenentf,löwej.rfcloning:arestriction-freemethodforinsertingtargetgenesintoplasmids[j].jbiochembiophysmethods,2006,67:67-74.
[13]  yangf,zhangs,tangw,etal.identificationoftheorotidine-5'-monophosphatedecarboxylasegeneoftheoleaginousyeastrhodosporidiumtoruloides[j].yeast,2008,25:623-630.
[14]  marquesrb,aghaia,deriddercm,etal.highefficacyofcombinationtherapyusingpi3k/aktinhibitorswithandrogendeprivationinprostatecancerpreclinicalmodels[j].eururol,2015,67:1177-1185.
[15]  liul,dongx.compleximpactsofpi3k/aktinhibitorstoandrogenreceptorgeneexpressioninprostatecancercells[j].plosone,2014,9:e108780.
[16]  lij,liur,yangy,etal.triptolide-inducedinvitroandinvivocytotoxicityinhumanbreastcancerstemcellsandprimarybreastcancercells[j].oncolrep,2014,31:2181-2186.
[17]  zhangt,hamzaa,caox,etal.anovelfsp90inhibitortodisrupthsp90/cdc37complexagainstpancreaticcancercells[j].molcancerther,2008,7:162-170.
[18]  liw,liuy,lixx,etal.mapksarenotinvolvedintriptolide-inducedcellgrowthinhibitionandapoptosisinprostatecancercelllineswithdifferentp53status[j].plantamed,2011,77:27-31.
[19]  tamgueo,chaic.triptolideinhibitshistonemethyltransferaseezh2andmodulatestheexpressionofitstargetgenesinprostatecancercells[j].asianpacjcancerprev,2013,14:5663-5669.
[20]  zhangl,altuwaijris,dengf,etal.nf-kappabregulatesandrogenreceptorexpressionandprostatecancergrowth[j].amjpathol,2009,175:489-499.
[21]  yinjunl,jiej,yunguiw.triptolideinhibitstranscriptionfactornf-kappabandinducesapoptosisofmultiplemyelomacells[j].leukres,2005,29:99-105.
[22]  calastrettia,gattig,quaresminic,etal.down-modulationofbcl-2sensitizespten-mutatedprostatecancercellstostarvationandtaxanes[j].prostate,2014,74:1411-1422.
[23]  shiotam,yokomizoa,naitos.increasedandrogenreceptortranscription:acauseofcastration-resistantprostatecancerandapossibletherapeutictarget[j].jmolendocrinol,2011,47:r25-r41.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133