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!"#$10005404 2014 20211305 !" Carfilzomib #$%&'()*+,-./01234 ! " #$% &'( )*+ ,-. / 0 400016!"!"#$%&'()*#+,-.$ /0 .$ 56%& 12 carfilzomib CFZ 3456789:;<=>?@AB'( BALB/c CDEFGHCDI -J C26 KLMN56789OPQ 40 R BALB/C CDSTAUVWXYZ[\]HC )、 CFZ ^_]CP )、 CFZ ` a]CT )、 789]CC ), b] 10 Rcdefgh9g?ijklmGHn) 12 o CP CT]Ypqrst CFZ ) 19 ouvwxyzgCD{-<569gdg56h|ELISAX}d~~ qRT PCR Westernblot }d{-< ATF2 pATF2 MAFbx MuRFl mRNA)* CD9g{-<9g HC ] >CP ] >CT ] >CC ]<005 ), 569gh| CC] >CT ] >CP ]<005 ); ~~{- < ATF2 MuRFl MAFbxmRNA?9 HC ] >CP ] >CT ] >CC]<005 ), pATF2 ATF2 CP ] CT ] >HC ] >CC ]<005 )。)+ CFZ 3456789CD:;<=>B pATF2 4~ Bh5678956789Carfilzomib  ¡ ATF2~h :;<1=>R730.6 R966 R977.3   ?@ABCDEFG¢ £Email tanglihua6969@sina.com HIJKhttp //www.cnki.net/kcms/detail/51.1095.R.20140821.1521.037.html 20140821 Carfilzomibamelioratesskeletalmuscleconsumptioninmicewithcancercachexia anditsmolecularmechanism WangQiang ZhengYueyong PengXudong KangQingjie DengDawei TangHua DepartmentofGastrointestinal Surgery DepartmentofHepatobiliarySurgery theFirstAffiliatedHospitalofChongqingMedicalUniversity Chongqing 400016 China Abstract Objective Tostudytheroleofcarfilzomib CFZ intheameliorationofskeletalmuscle consumptionincancercachexiaanditsassociatedmechanism. Methods Cancercachexiamodelwasinduced byinjectingmurinecolon26adenocarcinomacellsintomaleBALB/cmiceintraperitoneally.BALB/cmice weredividedinto4groupsrandomly includingahealthycontrolgroup HC ), aCFZpreventiongroup CP ), aCFZtreatmentgroup CT andacancercachexiagroup CC .Atdifferenttimepoints foodintake body weightandspontaneousactivityweredetected.FollowingadministrationofCFZintraperitoneallytwiceaweekto CPandCTgroupsonthedays5and12aftertumorcellsinjection respectively allmiceweresacrificedonday 19.Mousebody tumorentityandgastrocnemiusmuscleontheleftsidewereaccuratelyweighedandthe volumeoftumorsweremeasured.Theserumlevelsofreninandangiotensin weredetectedbyELISA.The mRNAandproteinlevelsofATF2 pATF2 MAFbxandMuRFlweredetectedbyrealtimePCRandWestern blotting. Results ComparedwiththeCCgroup theweightofmousebodyandgastrocnemiusmusclewere bothincreasedintheCPgroupandCTgroup<005 ), whichwerestilllowerthanthatoftheHCgroup <005 .ThetumormassandvolumeoftheCTgroupweregreaterthanthatoftheCPgroup lessthanthat oftheCCgroup <005 .ComparedwiththeCCgroup thelevelsofreninandangiotensin intheserum andthemRNAandproteinexpressionofATF2 MuRFlandMAFbxingastrocnemiusmuscleoftheCPandCT groupweredecreased however theratioofpATF2toATF2wereincreased.Theaboveresultshadstatistical significancebetweentheCPgroupandtheCTgroup<005 Conclusion CFZamelioratesskeletal muscleconsumptionincancercachexiamice whichmayberelatedtotheinhibitionofpATF2degradation resultinginsynthesisblockofreninangiotensinsystemandthesuppressionofubiquitinproteasomepathwayand tumorgrowth. ) 36 ¤) 20 ¥ 2014 ¦ 10 § 30 ¨ ) © ª # % & & « J Third Mil Med Univ Vol.36 No.20 Oct.30 2014

tmmu.edu.cnaammt.tmmu.edu.cn/Upload/PaperUpLoad/357d728b-defd-421d...HC] 24.85±1.36 137.5±13.29 CP] 22.50±1.36 a 110.8±13.70 a 2.26±0.36 a 2.54±0.41 a

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Page 1: tmmu.edu.cnaammt.tmmu.edu.cn/Upload/PaperUpLoad/357d728b-defd-421d...HC] 24.85±1.36 137.5±13.29 CP] 22.50±1.36 a 110.8±13.70 a 2.26±0.36 a 2.54±0.41 a

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CarfilzomibamelioratesskeletalmuscleconsumptioninmicewithcancercachexiaanditsmolecularmechanismWangQiang1,ZhengYueyong1,PengXudong1,KangQingjie1,DengDawei2,TangHua1(1DepartmentofGastrointestinalSurgery,2DepartmentofHepatobiliarySurgery,theFirstAffiliatedHospitalofChongqingMedicalUniversity,Chongqing,400016,China)

  [Abstract] Objective Tostudytheroleofcarfilzomib(CFZ)intheameliorationofskeletalmuscleconsumptionincancercachexiaanditsassociatedmechanism.Methods Cancercachexiamodelwasinducedbyinjectingmurinecolon26adenocarcinomacellsintomaleBALB/cmiceintraperitoneally.BALB/cmiceweredividedinto4groupsrandomly,includingahealthycontrolgroup(HC),aCFZpreventiongroup(CP),aCFZtreatmentgroup(CT)andacancercachexiagroup(CC).Atdifferenttimepoints,foodintake,bodyweightandspontaneousactivityweredetected.FollowingadministrationofCFZintraperitoneallytwiceaweektoCPandCTgroupsonthedays5and12aftertumorcellsinjection,respectively,allmiceweresacrificedonday19.Mousebody,tumorentityandgastrocnemiusmuscleontheleftsidewereaccuratelyweighedandthevolumeoftumorsweremeasured.TheserumlevelsofreninandangiotensinⅡ weredetectedbyELISA.ThemRNAandproteinlevelsofATF2,pATF2,MAFbxandMuRFlweredetectedbyrealtimePCRandWesternblotting.Results ComparedwiththeCCgroup,theweightofmousebodyandgastrocnemiusmusclewerebothincreasedintheCPgroupandCTgroup(P<005),whichwerestilllowerthanthatoftheHCgroup(P<005).ThetumormassandvolumeoftheCTgroupweregreaterthanthatoftheCPgroup,lessthanthatoftheCCgroup(P<005).ComparedwiththeCCgroup,thelevelsofreninandangiotensinⅡ intheserumandthemRNAandproteinexpressionofATF2,MuRFlandMAFbxingastrocnemiusmuscleoftheCPandCTgroupweredecreased,however,theratioofpATF2toATF2wereincreased.TheaboveresultshadstatisticalsignificancebetweentheCPgroupandtheCTgroup(P<005).Conclusion CFZamelioratesskeletalmuscleconsumptionincancercachexiamice,whichmayberelatedtotheinhibitionofpATF2degradationresultinginsynthesisblockofreninangiotensinsystemandthesuppressionofubiquitinproteasomepathwayandtumorgrowth.

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Page 2: tmmu.edu.cnaammt.tmmu.edu.cn/Upload/PaperUpLoad/357d728b-defd-421d...HC] 24.85±1.36 137.5±13.29 CP] 22.50±1.36 a 110.8±13.70 a 2.26±0.36 a 2.54±0.41 a

  [Keywords] cancercachexia;carfilzomib;phosphoATF2;reninangiotensinsystem;ubiquitinproteasomepathway

Correspondingauthor:TangHua,Email:tanglihua6969@sina.com

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[1]FearonK,StrasserF,AnkerSD,etal.Definitionandclassificationofcancercachexia:aninternationalconsensus[J].LancetOncol,2011,12(5):489-495.

[2]vonHaehlingaS,AnkerSD.Cachexiaasmajorunderestimatedunmetmedicalneed:factsandnumbers[J].IntJCardiol,2012,161(3):121-123.

[3]KumarNB,KaziA,SmithT,etal.Cancercachexia:traditionaltherapiesandnovelmolecularmechanismbasedapproachestotreatment[J].CurrTreatOptionsOncol,2010,11(3/4):107-117.

[4]PolgeC,HengAE,JarzaguetM,etal.MuscleactinispolyubiquitinylatedinvitroandinvivoandtargetedforbreakdownbytheE3ligaseMuRF1[J].FASEBJ,2011,25(11):3790-3802.

[5]RajanV,MitchWE.Ubiquitin,proteasomesandproteolyticmechanismsactivatedbykidneydisease[J].BiochimBiophysActa,2008,1782(12):795-799.

[6]DuJ,HuZ,MitchWE.Cellularsignalsactivatingmuscleproteolysisinchronickidneydisease:atwostageprocess[J].IntJBiochemCellBiol,2005,37(10):2147-2155.

[7]DeschM,HackmayerG,TodorovVT.IdentificationofATF2asatranscriptionalregulatorofreningene[J].BiolChem,2012,393(1/2):93-100.

[8]KhanML,StewartAK.Carfilzomib:anovelsecondgenerationproteasomeinhibitor[J].FutureOncol,2011,7(5):607-612.

[9]DemoSD,KirkCJ,AujayMA,etal.AntitumoractivityofPR171,anovelirreversibleinhibitoroftheproteasome[J].CancerRes,2007,67(13):6383-6391.

[10]JakubowiakAJ.Evolutionofcarfilzomibdoseandscheduleinpatientswithmultiplemyeloma:ahistoricaloverview[J].CancerTreatRev,2014,40(6):781-790.

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Page 5: tmmu.edu.cnaammt.tmmu.edu.cn/Upload/PaperUpLoad/357d728b-defd-421d...HC] 24.85±1.36 137.5±13.29 CP] 22.50±1.36 a 110.8±13.70 a 2.26±0.36 a 2.54±0.41 a

[11]DasmahapatraG,LemberskyD,SonMP,etal.ObatoclaxinteractssynergisticallywiththeirreversibleproteasomeinhibitorcarfilzomibinGCandABCDLBCLcellsinvitroandinvivo[J].MolCancerTher,2012,11(5):1122-1132.

[12]MansourMA,AljoufiMA,AlHosainiK,etal.Possibleroleofselective,irreversible,proteasomeinhibitor(carfilzomib)inthetreatmentofrathepatocellularcarcinoma[J].ChemBiolInteract,2014,215:17-24.

[13]GozdeckaM,BreitwieserW.TherolesofATF2(activatingtranscriptionfactor2)intumorigenesis[J].BiochemSocTrans,2012,40

(1):230-234.[14]YoshidaT,TabonyAM,GalvezS,etal.Molecularmechanismsand

signalingpathwaysofangiotensinIIinducedmusclewasting:potentialtherapeutictargetsforcardiaccachexia[J].IntJBiochemCellBiol,2013,45(10):2322-2332.

[15]LiS,WangX,LiY,etal.Bortezomib,aproteasomeinhibitor,attenuatesangiotensinIIinducedhypertensionandaorticremodelinginrats[J].PLoSOne,2013,8(10):e78564.

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