gabab受体激活对乳腺癌细胞mdamb231中pi3kakt和rasraferk信号的影响-effect of gabab receptor activation on pi 3 kakt and rasrafierk signals in breast cancer cell md amb 231.docx

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gabab受体激活对乳腺癌细胞mdamb231中pi3kakt和rasraferk信号的影响-effect of gabab receptor activation on pi 3 kakt and rasrafierk signals in breast cancer cell md amb 231.docx

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gabab受体激活对乳腺癌细胞mdamb231中pi3kakt和rasraferk信号的影响-effect of gabab receptor activation on pi 3 kakt and rasrafierk signals in breast cancer cell md amb 231

关键词：GABAB 受体，人乳腺癌细胞MDA-MB-231，PI3K，Akt，ERKAbstractGABABreceptorsaremembersofclassCfamilyofGproteincoupledreceptors,and theirligandisinhibitoryneurotransmittergamma-aminobutyricacid(GABA)ofthecentral nervoussystem.itiswidelydistributedinthemammaliancentralnervoussystemand GABAalsoexistsinvarioustissuesoutsidethecentralnervoussystem.Thereceptorsfor GABAincludetwotypeswhichGABAA andGABACreceptorsareionotropicmedicated fast GABAreaction, GABAB receptor is metabotropic which medicated slow GABA recation.GABAB receptorsconsistofGABAB1 andGABAB2 subunitsandexercisethe functionoftheheterodimer.GABABreceptorcanregulateproliferationandmigrationof varietytumorcell,butthemechanismisnotclear.PI3K/Aktsignalingpathwayplaysan importantroleintumordevelopmentandoccurrence.PI3Ks(phosphatidylinositol3-kinases) isanimportantkinaseintheintracellularwhichisdividedintothreecategories:classI, classIIandclassIII,thatarecompositedofvariouscatalyticsubunitandregulatory subunit.Catalyticsubunitp110αandp110δcanbeactivatedbyreceptortyrosinekinase (RTK),p110γonlybeactivatedbyGPCRandthep110βcanbeactivatedbyRTKor GPCR.PI3K/Aktsignalingpathwaycanpromotecellgrowth,survivalandproliferation, which is abnormallyactivated in tumor cells.Theclassical mitogen-activated protein kinase (MAPK)pathway (Raf/MEK/ERK), activated by cell surface receptor tyrosine kinases (RTKs)followinggrowthfactor binding,regulatescell proliferation.Activation of theRaf/ MEK/ERK pathwayis afrequentevent in different humancancers.Inthispaper,InvestigatingGABABreceptorsinfluncetheactivationofPI3K/Aktand Raf/MEK/ERKpathwayinthehumanbreastcancercelllineMDA-MB-231andgranule neuronsinmicecellsare.GABABreceptorspecificallostericmodulatorCGP7930wasused to treat breast cancer cells MDA-MB-231 for ashort time, and the result showed theAktandERKwasactivatedbyGABABreceptors.thebreastcancercellline MDA-MB-231wastreatedwithGABABreceptoragonistBaclofenandallosteric modulatorCGP7930,MTTmethodshowthatBaclofencaninhibittheproliferationof MDA-MB-23