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穿心莲内酯衍生物ADS体外抗肿瘤作用机制研究 Abstract ADS,aderivativeofTriptolidefromTripterygiumwilfordii,hasbeenwidelystudiedforitsanti-tumoractivity.Inthisstudy,weinvestigatedthemechanismsbywhichADSexertsitsanti-tumoreffectsinvitro.WefoundthatADSinhibitscellproliferation,inducescellcyclearrest,andpromotesapoptosisincancercells.Furthermore,ADSwasshowntosuppresstheexpressionofvariousoncogenicproteinsandactivatevarioustumorsuppressorproteins,indicatingthatitsanti-tumoreffectsaremediatedthroughregulationofmultiplesignalingpathways.ThesefindingssuggestthatADSisapromisingcandidateforthedevelopmentofnovelanti-cancertherapeutics. Introduction Cancerisoneofthemostcommonanddeadlydiseasesworldwide,withhighmorbidityandmortalityrates.Althoughsignificantprogresshasbeenmadeinthetreatmentofcancer,themorbidityandmortalityratesremainhigh.Therefore,itisimportanttoidentifynewtherapeuticagentsthatcaneffectivelyinhibittumorgrowthandmetastasis. TriptolideisanaturalcompoundderivedfromTripterygiumwilfordiiHookF(TwHF),atraditionalChinesemedicinethathasbeenusedforthousandsofyearstotreatvariousdiseases.Ithasbeenshowntohaveanti-inflammatory,immunosuppressive,andanti-tumoreffects.However,theclinicalapplicationoftriptolideislimitedduetoitstoxicityandsideeffects. ADS,aderivativeofTriptolide,hasbeenshowntohavelowertoxicityandgreateranti-tumoractivitythanTriptolideinmultiplecancercelllines.However,theunderlyingmechanismsoftheanti-tumoreffectsofADSremainunclear.Inthisstudy,weinvestigatedthemechanismsbywhichADSexertsitsanti-tumoreffectsinvitro. MaterialsandMethods Cellcultureandreagents HumanprostatecancercelllinePC-3andhumanbreastcancercelllineMDA-MB-231wereobtainedfromtheAmericanTypeCultureCollection(ATCC).ADSwasobtainedfromSigma-Aldrich(St.Louis,MO,USA).Cellculturemedium,fetalbovineserum,andotherreagentswereobtainedfromGibco(GrandIsland,NY,USA). Cellproliferationassay CellproliferationwasmeasuredusingtheMTTassay.Cellswereseededin96-wellplatesandtreatedwithdifferentconcentrationsofADSfor24,48or72hours.TheMTTreagentwas