Nuclear Factor-Kappa B Inhibition Can Enhance Apoptosis of Differentiated Thyroid Cancer Cells Induced by 131I 英文参考文献.docVIP

Nuclear Factor-Kappa B Inhibition Can Enhance Apoptosis of Differentiated Thyroid Cancer Cells Induced by 131I 英文参考文献.doc

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Nuclear Factor-Kappa B Inhibition Can Enhance Apoptosis of Differentiated Thyroid Cancer Cells Induced by 131I 英文参考文献

NuclearFactor-KappaBInhibitionCanEnhance ApoptosisofDifferentiatedThyroidCancerCellsInduced by 131I ZhaoweiMeng1*.,ShanshanLou1,2.,JianTan1,KeXu3,QiangJia1,WeiZheng1 1DepartmentofNuclearMedicine,TianjinMedicalUniversityGeneralHospital,Tianjin,People’sRepublicofChina,2TianjinNormalUniversity,Tianjin,People’sRepublic of China, 3Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin,People’sRepublicofChina Abstract Objective:Toevaluatechangesofnuclearfactor-kappaB(NF-kB)duringradioiodine131(131I)therapyandwhetherNF-kB inhibitioncouldenhance 131I-inducedapoptosisindifferentiatedthyroidcancer(DTC)cellsinasynergisticmanner. Methods:ThreehumanDTCcelllineswereused.NF-kBinhibitionwasachievedbyusingaNF-kBinhibitor(Bay11-7082)or by p65 siRNA transfection. Methyl-thiazolyl-tetrazolium assay was performed for cell viability assessment. DNA-binding assay,luciferasereporterassay,andWesternblotwereadoptedtodeterminefunctionandexpressionchangesofNF-kB. ThenNF-kBregulatedanti-apoptoticfactorsXIAP,cIAP1,andBcl-xLweremeasured.ApoptosiswasanalyzedbyWestern blotforcaspase3andPARP,andbyflowcytometryaswell.Aniodideuptakeassaywasperformedtodeterminewhether NF-kBinhibitioncouldinfluenceradioactiveiodideuptake. Results:Themethyl-thiazolyl-tetrazoliumassayshowedsignificantdecreaseofviablecellsbycombinationtherapythanby mono-therapies.TheDNA-bindingassayandluciferasereporterassayshowedenhancedNF-kBfunctionandreportergene activitiesdueto 131I,yetsignificantsuppressionwasachievedbyNF-kBinhibition.Westernblotproved 131Icouldincrease nuclear NF-kB concentration, while NF-kB inhibition reduced NF-kB concentration. Western blot also demonstrated significant up-regulation of XIAP, cIAP1, and Bcl-xL after 131I therapy. And inhibition of NF-kB could significantly down- regulate these factors. Finally, synergism induced by combined therapy was displayed by significant enhancements of cleave

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