Schisandrin B Attenuates Cancer Invasion and Metastasis Via Inhibiting Epithelial-Mesenchymal Transition 英文参考文献.docVIP

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Schisandrin B Attenuates Cancer Invasion and Metastasis Via Inhibiting Epithelial-Mesenchymal Transition 英文参考文献.doc

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Schisandrin B Attenuates Cancer Invasion and Metastasis Via Inhibiting Epithelial-Mesenchymal Transition 英文参考文献

SchisandrinBAttenuatesCancerInvasionandMetastasis ViaInhibitingEpithelial-MesenchymalTransition ZhenLiu1.,BiaoZhang1.,KunLiu2,ZonghuiDing1,XunHu1* 1CancerInstitute(KeyLaboratoryforCancerInterventionandPreventionofChinaNationalMinistryofEducation),TheSecondAffiliatedHospital,ZhejiangUniversity SchoolofMedicine,Hangzhou,China,2SecondDepartmentofGeneralSurgery,SirRunRunShawHospital,ZhejiangUniversitySchoolofMedicine,Zhangjiang,People’s RepublicofChina Abstract Background: Metastasis is the major cause of cancer related death and targeting the process of metastasis has been proposedasastrategytocombatcancer.Therefore,todevelopcandidatedrugsthattargettheprocessofmetastasisisvery important. In the preliminary studies, we found that schisandrin B (Sch B), a naturally-occurring dibenzocyclooctadiene lignanwithverylowtoxicity,couldsuppresscancermetastasis. Methodology:BALB/cmicewereinoculatedsubcutaneouslyorinjectedviatailveinwithmurinebreastcancer4T1cells. Mice were divided into Sch B-treated and control groups. The primary tumor growth, local invasion, lung and bone metastasis, and survival time were monitored. Tumor biopsies were examined immuno- and histo-pathologically. The inhibitory activity of Sch B on TGF-b induced epithelial-mesenchymal transition (EMT) of 4T1 and primary human breast cancercellswasassayed. PrincipalFindings:SchBsignificantlysuppressedthespontaneouslungandbonemetastasisof4T1cellsinoculateds.c. withoutsignificanteffectonprimarytumorgrowthandsignificantlyextendedthesurvivaltimeofthesemice.SchBdidnot inhibitlungmetastasisof4T1cellsthatwereinjectedviatailvein.DelayedstartoftreatmentwithSchBinmicewithpre- existing tumors did not reduce lung metastasis. These results suggested that Sch B acted at the step of local invasion. HistopathologicalevidencesdemonstratedthattheprimarytumorsinSchBgroupweresignificantlylesslocallyinvasive thancontroltumors.InvitroassaysdemonstratedthatSchBcouldinhibitTGF-binducedEMTof4T1cellsandofprimary humanbreastcancercells. C