Estrogen Induced Metastatic Modulators MMP-2 and MMP-9 Are Targets of 3,3′-Diindolylmethane in Thyroid Cancer 英文参考文献.docVIP

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Estrogen Induced Metastatic Modulators MMP-2 and MMP-9 Are Targets of 3,3′-Diindolylmethane in Thyroid Cancer 英文参考文献.doc

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Estrogen Induced Metastatic Modulators MMP-2 and MMP-9 Are Targets of 3,3′-Diindolylmethane in Thyroid Cancer 英文参考文献

EstrogenInducedMetastaticModulatorsMMP-2and MMP-9AreTargetsof3,39-DiindolylmethaneinThyroid Cancer ShilpiRajoria1,RobertSuriano1,AndreaGeorge1,ArulkumaranShanmugam1,StimsonP.Schantz2 ,Jan Geliebter1,RajK.Tiwari1* 1DepartmentofMicrobiologyandImmunology,NewYorkMedicalCollege,Valhalla,NewYork,UnitedStatesofAmerica,2DepartmentofOtolaryngology,NewYorkEye andEarInfirmary,NewYork,NewYork,UnitedStatesofAmerica Abstract Background:Thyroidcanceristhemostcommonendocrinerelatedcancerwithincreasingincidencesduringthepastfive years.Currenttreatmentsforthyroidcancer,suchassurgeryorradioactiveiodinetherapy,oftenrequirepatientstobeon lifelongthyroidhormonereplacementtherapyandgiventhesignificantrecurrenceratesofthyroidcancer,newpreventive modalities are needed. The present study investigates the property of a natural dietary compound found in cruciferous vegetables, 3,39-diindolylmethane(DIM),totarget themetastatic phenotype ofthyroid cancer cells through a functional estrogenreceptor. Methodology/PrincipalFindings:Thyroidcancercelllinesweretreatedwithestrogenand/orDIMandsubjectedtoinvitro adhesion,migrationandinvasionassaystoinvestigatetheanti-metastaticandanti-estrogeniceffectsofDIM.Weobserved thatDIMinhibitsestrogenmediatedincreaseinthyroidcellmigration,adhesionandinvasion,whichisalsosupportedby ER-a downregulation (siRNA) studies. Western blot and zymography analyses provided direct evidence for this DIM mediated inhibition of E2 enhanced metastasis associated events by virtue of targeting essential proteolytic enzymes, namelyMMP-2andMMP-9. Conclusion/Significance: Our data reports for the first time that DIM displays anti-estrogenic like activity by inhibiting estradiolenhancedthyroidcancercellproliferationandinvitrometastasisassociatedevents,namelyadhesion,migration and invasion. Most significantly, MMP-2 and MMP-9, which are known to promote and enhance metastasis, were determinedtobetargetsofDIM.Thisanti-estrogenlikepropertyofDIMmayleadtothedevelopmentofanovelpreventive a