IGF-IR单克隆抗体对Jurkat细胞株增殖及凋亡的影响的综述报告.docx
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IGF-IR单克隆抗体对Jurkat细胞株增殖及凋亡的影响的综述报告.docx

IGF-IR单克隆抗体对Jurkat细胞株增殖及凋亡的影响的综述报告.docx

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IGF-IR单克隆抗体对Jurkat细胞株增殖及凋亡的影响的综述报告IGF-IR单克隆抗体对Jurkat细胞株增殖及凋亡的影响的综述报告概述:Theinsulin-likegrowthfactorreceptor(IGF-IR)isatransmembranereceptorproteinthatplaysanimportantroleincellproliferation,differentiation,andsurvival.Itisamemberofthetyrosinekinasereceptorfamilyandisactivatedbybindingtoinsulin-likegrowthfactors(IGFs)suchasIGF-IandIGF-II.IGF-IRhasbeenimplicatedinthedevelopmentandprogressionofvariouscancers,includingleukemia.Inthisreview,wewillfocusontheeffectofmono-clonalantibodiestargetingIGF-IRontheproliferationandapoptosisofJurkatcells,aleukemiacellline.JurkatcellsarederivedfromhumanTcellleukemiaandarewidelyusedasamodelforstudyingTlymphocytebiology.ThecellsrequireIL-2forgrowthandarehighlysensitivetoapoptosis-inducingstimuli.IGF-IRisexpressedonthesurfaceofJurkatcellsandhasbeenshowntoplayaroleintheirproliferationandsurvival.Mono-clonalantibodiestargetingIGF-IRhavebeendevelopedascancertherapeutics.TheseantibodiesbindtoIGF-IRandblockitsactivationbyIGFs,leadingtoinhibitionofdownstreamsignalingpathwayssuchasPI3K-AktandMAPK-ERK.SeveralstudieshaveinvestigatedtheeffectofIGF-IRmono-clonalantibodiesonJurkatcellsandhaveyieldedconflictingresults.EffectofIGF-IRmono-clonalantibodiesonJurkatcellproliferation:SeveralstudieshaveshownthattreatmentwithIGF-IRmono-clonalantibodiesinhibitsJurkatcellproliferation.OnestudyfoundthattreatmentwiththeantibodyMK-0646reducedtheproliferationofJurkatcellsinadose-dependentmanner,withasignificantdecreaseobservedatconcentrationsof10-100nM(1).AnotherstudyfoundthattreatmentwiththeantibodyAMG479inhibitedtheproliferationofJurkatcellsinadose-dependentmanner,withasignificantdecreaseobservedatconcentrationsof10-30nM(2).Inbothstudies,theinhibitionofcellproliferationwasassociatedwithadecreaseintheactivationofthePI3K-AktandMAPK-ERKpathways.However,otherstudieshavereportedthatIGF-IRmono-clonalantibodieshavenoeffectonJurkatcellproliferation.OnestudyfoundthattreatmentwiththeantibodyIMC-A12hadnoeffectontheproliferationofJurkatcells,evenatconcentrationsash
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