title: Fluoxetine induces preventive and complex effects against colon cancer development in epithelial and stromal areas in rats.
abstract: Fluoxetine (FLX) is a drug commonly used as antidepressant. However, its effects on tumorigenesis remain controversial. Aiming to evaluate the effects of FLX treatment on early malignant changes, we analyzed serotonin (5-HT) metabolism and recognition, aberrant crypt foci (ACF), proliferative process, microvessels, vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) expression in colon tissue. Male Wistar rats received a daily FLX-gavage (30mgkg(-1)) and, a single dose of 1,2 dimethylhydrazine (DMH; i.p., 125mgkg(-1)). After 6 weeks of FLX-treatment, our results revealed that FLX and nor-fluoxetine (N-FLX) are present in colon tissue, which was related to significant increase in serotonin (5-HT) levels (P<0.05) possibly through a blockade in SERT mRNA (serotonin reuptake transporter; P<0.05) resulting in lower 5-hydroxyindoleacetic acid (5-HIAA) levels (P<0.01) and, 5-HT2C receptor mRNA expressions. FLX-treatment decreased dysplastic ACF development (P<0.01) and proliferative process (P<0.001) in epithelia. We observed a significant decrease in the development of malignant microvessels (P<0.05), VEGF (P<0.001), and COX-2 expression (P<0.01). These findings suggest that FLX may have oncostatic effects on carcinogenic colon tissue, probably due to its modulatory activity on 5-HT metabolism and/or its ability to reduce colonic malignant events.
authors.affiliation: Department of Pathology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14049-900, Brazil. kannen71@yahoo.com
authors.forename: Vinicius
authors.initials: V
authors.lastname: Kannen
authors.forename: Tassiana
authors.initials: T
authors.lastname: Marini
authors.forename: Aline
authors.initials: A
authors.lastname: Turatti
authors.forename: Milene C
authors.initials: MC
authors.lastname: Carvalho
authors.forename: Marcus L
authors.initials: ML
authors.lastname: Brandão
authors.forename: Valquiria A P
authors.initials: VA
authors.lastname: Jabor
authors.forename: Pierina S
authors.initials: PS
authors.lastname: Bonato
authors.forename: Frederico R
authors.initials: FR
authors.lastname: Ferreira
authors.forename: Dalila L
authors.initials: DL
authors.lastname: Zanette
authors.forename: Wilson A
authors.initials: WA
authors.lastname: Silva
authors.forename: Sérgio B
authors.initials: SB
authors.lastname: Garcia
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000032:analysis; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D011230:Precancerous Conditions / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D051546:Cyclooxygenase 2; D005473:Fluoxetine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D042461:Vascular Endothelial Growth Factor A