Antiproliferative Effects of Fluoxetine on Colon Cancer Cells and in a Colonic Carcinogen Mouse Model 英文参考文献.docVIP
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Antiproliferative Effects of Fluoxetine on Colon Cancer Cells and in a Colonic Carcinogen Mouse Model 英文参考文献
AntiproliferativeEffectsofFluoxetineonColonCancer
CellsandinaColonicCarcinogenMouseModel
ViniciusKannen1,2,HenningHintzsche2,DalilaL.Zanette3,WilsonA.Silva Jr.3,Se′rgioB.Garcia1 ,Ana
MariaWaaga-Gasser4,HelgaStopper2*
1Department of Pathology, Medical School of Ribeira?o Preto, University of Sa?o Paulo, Ribeira?o Preto, Brazil, 2Department of Toxicology, University of Wuerzburg,
Wuerzburg,Germany,3NationalInstituteofScienceandTechnologyinStemCellandCellTherapy,CNPq/FAPESP,DepartmentofGenetics,MedicalSchoolofRibeira?o
Preto,UniversityofSa?o Paulo,Ribeira?o Preto,Brazil,4DepartmentofSurgeryI,MolecularOncologyandImmunology,UniversityofWuerzburg,Wuerzburg,Germany
Abstract
Theantidepressantfluoxetinehasbeenunderdiscussionbecauseofitspotentialinfluenceoncancerrisk.Itwasfoundto
inhibitthedevelopmentofcarcinogen-inducedpreneoplasticlesionsincolontissue,butthemechanismsofactionarenot
wellunderstood.Therefore,weinvestigatedanti-proliferativeeffects,andusedHT29colontumorcellsinvitro,aswellas
C57BL/6 mice exposed to intra-rectal treatment with the carcinogen N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) as
models. Fluoxetine increased the percentage of HT29 cells in the G0/G1 phase of cell-cycle, and the expression of p27
protein. This was not related to an induction of apoptosis, reactive oxygen species or DNA damage. In vivo , fluoxetine
reduced the development of MNNG-induced dysplasia and vascularization-related dysplasia in colon tissue, which was
analyzed by histopathological techniques. An anti-proliferative potential of fluoxetine was observed in epithelial and
stromalareas.ItwasaccompaniedbyareductionofVEGFexpressionandofthenumberofcellswithangiogenicpotential,
suchasCD133,CD34,andCD31-positivecellclusters.Takentogether,ourfindingssuggestthatfluoxetinetreatmenttargets
stepsofearlycoloncarcinogenesis.Thisconfirmsitsprotectivepotential,explainingatleastpartiallythelowercoloncancer
riskunderantidepressanttherapy.
Citation:KannenV,HintzscheH,ZanetteDL,SilvaWAJr,Garci
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