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