新合成靛玉红类化合物的抗肿瘤作用与其机制

《新合成靛玉红类化合物的抗肿瘤作用与其机制》由会员上传分享，免费在线阅读，更多相关内容在行业资料-天天文库。

1、江苏大学硕士学位论文ABSTRACTobject：Anti—tumoreffectsandpossiblemechanismsofaseriesofnovelsynthesizedindirubincompoundswereinvestigated，whichwillcontributetodevelopnewanticanceragentswitllSelf-dominatedIntellectualPropertyRight．Methods：Antitumoractivityof44kindsofcompoundswerescreened，andindole-3-deriva

2、teAwasaccepted．ThemodelofHepSxenograftswasusedtoevaluatetheantitumoreffectinvivo．FourhumancancercelllinesSGC，HepG2，Hela，A549cellswereexposedtoindole一3-derivateAfor48h，cellsproliferationweredetectedbyMTTassayandthe50％inhibitoryconcentration(ICs0)Wascalculated．Thenindole-3-derivateAWaschosentoi

3、nvestigateforitseffectandmechanismofantitumor．CellcycleWasanalyzedfollowingPIstaining．ThemorphologicalandnucleichangesinH2B--GFP·-labledHeLacellswereobservedbyusingalivecellsystem(LCS)andstained埘t11DAPI．CellapoptosiswasdetectedbyAnnexin—V／PIstaining．Someindexofmitochondfialfunctionlikeintrace

4、llularROSlevel，mitochondrialmembranepotential，intracellularfreeCa+contentweredetected晰thDCFH-DA，JC-1，Fluo-3／AMstaining，respectively．MeanwhileATPcontentandoxygenconsumptionweredetectedbyluciferaseassayandClarkoxygenelectrode．Theexpressionlevelofcdc2，cyclinB1，Bcl一2，Baxandactivationofcaspase3，8，

5、9wereexaminedbyWesternblot．MitochondrialswellingWasusedtodeterminetheinteractionbetweenmitochondriaandindole．3．derivateA．Results：Indole-3-derivateAexhibitedsignificantinhibitionofcellproliferationonofdifferentcellsandtheIC50ofwasamong4·13I．tmol／L．Indole．3．defivateAinhibittheproliferationofHep

6、G2cellsinadose—andtime—dependentway，andalsoinhibitthecolonyformation．Invivo，theanticanceractivityofindole一3一derivateAagainstHepSxenografisWasbetterthan5-FUandnoobviouslyadverseeffects．Indole一3-derivateAinducedcellcyclearrestinG2／Mphase．anddecreasedtheexpressionofcyclinB1andcdc2．Treatedwimindo

7、le-3-derivateA，itwasfoundthatearlyapoptoticcellsweresignificantlyincreasedandnucleusmorphologywereshowingpyknosisandfragmentation．Westernblotshowedthatindole一3一defiva：ceAactivatedcaspase3，8，9，andinducedcaspase-dependentapoptosis．whichalsoindi