简介:Theeffectandmechanismofcarmustine(BCNU)combinedwithall-transretinoicacid(ATRA)ontheapoptosisofhumanglioblastomaU251cellswereinvestigatedbymeansof3-(4,5-dimethylthiazol-2-yl)-2,5-diphe-nyltetrazoliumbromide(MTT)assay,flowcytometry,reversetranscription-polymerasechainreaction(RT-PCR)andWesternblotanalysis.TheresultsshowthatBCNUorATRAshowstime-anddose-dependentinhibitioneffectsonhumanglioblastomaU251cellsandthecombinationofBCNUwithATRAshowsansynergisticinhibitioneffectonhumanglioblastomaU251cells,andthecombinedBCNUandATRAcansignificantlyinhibittheproliferationofhumanglioblastomaU251cells,andinducetheapoptosisofthem,makingthecellsarrestinthestageofG1phase,thestageofSandG2phasesdecline,therateoftheapoptosisofhumanglioblastomaU251cellsincrease,thecorrespondingmRNAexpressionofcyclinEandcyclin-dependentkinase2(CDK2)downregulatedandthecorrespon-dingmRNAexpressionofp27kip1unregulated.Inaddition,thecombinedBCNUandATRAreducedtheproteinexpressionofnuclearfactorkappaB(NF-κB).Takentogether,theseresultssuggestthatthetreatmentofhumanglioblastomaU251cellswithacombinationapplicationofATRAandBCNUcanexertsynergisticeffect,thecourseofthiskindofcombinationchemotherapymaylikelybeassociatedwithmultiplemolecularmechanismsforapoptosis,furthermore,thecyclinEandp27kip1shouldbeconsideredasnoveltargetsforcontrollingthegrowthofglioblastomacells.