苦参碱调控p16ink4acyclind1cdk4通路干预n-matrine regulates the intervention of p 16 ink 4 acyclind 1 cdk 4 pathway n.docxVIP

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苦参碱调控p16ink4acyclind1cdk4通路干预n-matrine regulates the intervention of p 16 ink 4 acyclind 1 cdk 4 pathway n.docx

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苦参碱调控p16ink4acyclind1cdk4通路干预n-matrine regulates the intervention of p 16 ink 4 acyclind 1 cdk 4 pathway n

MatrinesuppressestumorinvasioninN-butyl-N-(4-hydroxybutyl)nitrosamine-inducedurinarybladdercancerviaregulationofp16INK4a/cyclinD1/CDK4pathwayABSTRACTObjectivesThisstudywasdesignedtoexploretheeffectandmolecularmechanismofmatrineonN-buthy1-N-(4-hydroxybuty1)nitrosamine(BBN)-inducedbladdercancerinrats,thepathwayofp16INK4a/cyclinD1/cdk4wereinvestigated.MethodsMaleSprague-Dawleyratswererandomlydividedintosixgroups,thecontrol,BBN,celecoxib,matrine(50,100and200mg·kg-1·d-1)group.ThebladdercancerwasinducedbydailyintragastricadministrationofN-bthyl-N-(4-hydroxybutyl)nitrosamine(BBN)(200mg·0.5ml-1)twiceaweekforeightweeksinSprague-Dawleyrats.OneweekbeforeadministrationofBBN,ratsweregivencelecoxib(500mg·kg-1·d-1)anddifferentdose(50,100and200mg·kg-1·d-1)ofmatrineorsalinebyintragastric,whereasthegroupwereonlyfedwithsalinefromthebeginning.Animalsweresacrificedattheendof35thweek,immunohistochemicalmethodwasusedtodetecttheexpressionofp16INK4a,andtheproteincontentofp16INK4a/cyclinD1/CDK4pathwayinbladdertissueweremeasuredbythemethodofWesternblot.ResultsComparedwithcontrolgroup,theproteinlevelofp16INK4awassignificantlyreducedinBBN-inducedbladdercancermodelgroup(P＜0.01),whiletheexpressionofcyclinD1andCDK4wereshowedmarkedlyincrease(P＜0.01).Matrine(200mg·kg-1·d-1)treatmentcouldincreasetheexpressionofp16INK4acomparedwithBBNgroup(P＜0.05).ComparedwithBBNgroup,Matrine(50and200mg·kg-1·d-1)treatmentgroupscouldreducetheexpressionofcyclinD1(P＜0.05),whereasCDK4alsoperformedasignificantdecrease(P＜0.05).ConclusionsOurresultssuggestthatmatrinehasaneffectagainsttheinvasionofbladdercancer.ThemolecularmechanismofmatrineagainsttheinvasionofbladdercancerinducedbyBBNisviatheregulationofp16INK4a/cyclinD1/CDK4pathway.KEYWORDSmatrine,BBN,bladdercancer,invasion,p16INK4a,cyclinD1,CDK4中英文缩略词表(Abbreviation)英文英文全称中文全称BBNN-bthy1-N-(4-hydroxybuty1)NitrosamineN-丁基-N-（4-羟丁基）亚硝胺CDK4CyclinD1-dependentkinase4细胞周期蛋白依赖性激酶4CKICyclin-dependentkinaseinhibitor细胞周期蛋白依赖性激酶抑制剂CyclinD1CyclinD1细胞周期蛋白D1DAB3,3-DiamineBenzidine二氨基联苯胺HR