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1、英文摘要蛋白酶体抑制剂MG132对非小细胞肺癌生长转移和放射敏感性的影响及机制TheeffectofproteasomeinhibitorMG132ongrowth,metastasis,radiotherapeuticefficacyinhunmannon-smallcelllungcancerAbstractObjectiveInthisstudy,theeffectofproteasomeinhibitorMG132atalowdoseongrowth,metastasis,apoptosis,cellcycled
2、istribution,radiotherapeuticefficacy,anditsaccuratemechanismofradiosensitizationwereinvestigatedinhumannon-smallcelllungcancer,invitroandinvivo.MethodsInvitro,afterA549andH1299cellsweretreatedwithMG132and/orIR,thecellviabilitywasdetectedbyMTTassay;Scratchmigratio
3、nassayandtranswellmigrationassaywereusedtodeterminethemigrationandinvasionabilityofA549andH1299cells;Clonogenicsurvivaldatawasobtainedtoassesseffectsoftreatmentonradiosensitization;Changesofcellapoptosisandcellcycledistributionwereanalyzedbyflowcytometryassay;The
4、proteinexpressionmodulatedbyMG132andIRwereinspectedbyWesternblotanalysis.Todetermineinvivoradiotherapeuticefficacy,tumorgrowthdelaywasanalyzedinaH1299tumor-bearingxenograftmousemodelafterrepeatedtreatmentofMG132and/orIR.ResultsMG132aloneinhibitedcellgrowthinA549a
5、ndH1299cells,inadose-andtime-dependentmanner(P<0.01);MG132atanon-toxicdoseenhancedtheradiation-inducedcytotoxicityofA549andH1299cells,inaradiationdose-andpretreatmenttime-dependentmanner(P<0.01);MG132incombinationwithradiationsignificantlysuppressedthemigrationan
6、dinvasionofA549andH1299cellscomparedtocontrol(P<0.05);MG132atanon-toxicdoseincombinationwithradiationresultedindecreasedclonogenicsurvivalandincreasedradiosensitivityofA549andH1299cells;MG132enhancedradiation-inducedapoptosisinA549andH1299cells(P<0.01);MG132enhan
7、cedradiation-inducedcellcyclearrestofG1inA549cells,andG2/MinH1299cells(P<0.05);TheexpressionofMMP-2.-9,Bcl-2wassignificantlysuppressedbyMG132incombinationwithradiationbothinA549andH1299cells,whiletheIV蛋白酶体抑制剂MG132对非小细胞肺癌生长转移和放射敏感性的影响及机制英文摘要expressionofBaxwasup-re
8、gulatedrelatively.InA549cells,theexpressionofcyclinD1wassignificantlydecreasedbyMG132incombinationwithradiation,accompanyingasignificantincreasedofP53expressio