Artículos de revistas
Fluoxetine induces preventive and complex effects against colon cancer development in epithelial and stromal areas in rats
Fecha
2011Registro en:
TOXICOLOGY LETTERS, v.204, n.2/Mar, p.134-140, 2011
0378-4274
10.1016/j.toxlet.2011.04.024
Autor
KANNEN, Vinicius
MARINI, Tassiana
TURATTI, Aline
CARVALHO, Milene C.
BRANDAO, Marcus L.
JABOR, Valquiria A. P.
BONATO, Pierina S.
FERREIRA, Frederico R.
ZANETTE, Dalila L.
SILVA JR., Wilson A.
GARCIA, Sergio B.
Institución
Resumen
Fluoxetine (FIX) is a drug commonly used as antidepressant. However, its effects on tumorigenesis remain controversial. Aiming to evaluate the effects of FIX 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 (30 mg kg(-1)) and, a single dose of 1.2 dimethylhydrazine (DMH; i.p., 125 mg kg(-1)). After 6 weeks of FIX-treatment, our results revealed that FIX and nor-fluoxetine (N-FIX) 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. FIX-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 FIX 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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.