gabab受体对乳腺癌细胞中pi3kakt信号通路的影响-effect of gabab receptor on pi 3 kakt signaling pathway in breast cancer cells.docx

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2018-06-04 发布于上海
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gabab受体对乳腺癌细胞中pi3kakt信号通路的影响-effect of gabab receptor on pi 3 kakt signaling pathway in breast cancer cells.docx

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gabab受体对乳腺癌细胞中pi3kakt信号通路的影响-effect of gabab receptor on pi 3 kakt signaling pathway in breast cancer cells

的增殖；Transwell实验结果表明，Baclofen可增强MDA-MB-231细胞的迁移，CGP7930则抑制细胞迁移，并呈浓度相关性。目前，尚未见到GABAB受体激活对乳腺癌细胞中PI3K/Akt信号通路、细胞增殖、迁移等影响的相关报道，因此，本研究为进一步探索GABAB受体通过偶联p110α激活Akt的分子机制提供了新的实验依据，同时，也为针对GABABR-p110偶联的抗肿瘤新药的筛选提供新的理论依据。关键词：GABAB受体，人乳腺癌细胞MCF-7 和MDA-MB-231，PI3K，Akt，p110αAbstractGamma-aminobutyricacid(GABA)isthemajorinhibitoryneurotransmitteranditis widelydistributedin the mammalian central nervous system.However,GABA alsoexistsin varioustissuesoutsidethecentralnervoussystem.ThereceptorsforGABAincludetwo types,GABAAandGABACreceptorsareionotropic,GABABreceptorismetabotropicand belongstotheG-proteincoupledreceptors(GPCR)family.Interestingly,asa neurotransmitterreceptor,GABABreceptorcanregulateavarietyoftumor cell proliferationandmigration,butthemechanismisnotclear.PI3K/Aktsignalingpathway playsanimportantroleintumordevelopment.PI3Ks(phosphatidylinositol3-kinases)are dividedinto threecategories(classI,IIandIII)based onthe structureand function.Class IA PI3Kscanbeactivatedbytyrosinekinases,ClassIBPI3KscanbeactivatedbyG protein-coupledreceptors,IAclassPI3Ksincludethecatalyticsubunitanddifferent regulatorysubunits,p110α,p110β,p110γ,p110δarecatalyticsubunits,p85α,p85β,p55γ are regulatorysubunits.PI3K/Aktsignalingpathwaycanpromotecellgrowth,proliferation and survival,whichisabnormallyactivatedintumorcells.Ithasbeenrevealedthatsome GPCRcanactivatePI3K/Aktsignalingpathway,butthereisnoreportregardingthe regulationofPI3K/Akt signaling pathway by GABABreceptor intumorcells.Inthisstudy,activationofPI3K/AktpathwayinucedbyGABAB receptorinhumanbreastcancercelllinesMCF-7andMDA-MB-231wasinvestigated.GABABreceptor specificallostericmodulatorCGP7930wasusedtotreatbreastcancercellsforashorttime, andtheresultshowedthatAktwastransientlyactivatedbyGABABreceptors.Akt phosphorylationreachedthehighestlevelatthetimepointof30minutes,andthen decreasedgradually.However,whetherGABABreceptorcandirectlythroughPI3Ks catalyticsubunitp110αorp110γworkorthroughtransactivionofRTKandthenactivate Aktbyp110α,p110β,p110δisno