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.

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Physical exercise has proven protective against colon carcinogenesis. We sought to clarify whether the frequency and duration of physical training were key factors for its anticarcinogenic effects on the colon. Either sedentary or physically trained male Wistar rats (n=82) were either exposed or not to the carcinogen dimethylhidrazine (DMH). The first protocol investigated whether swimming for 60 min in different frequencies modulates antipreneoplastic effects of physical training. Another protocol then explored whether the duration for training 5 times a week impacts on the development of colon preneoplastic lesions. After 8 weeks, serum and colon samples were collected and analyzed afterwards. Swimming once a week for 60 min did not promote those anticarcinogenic effects found in rats trained 5 times weekly. Such weekly sustained physical training not only decreased the development of colon preneoplastic, but also epithelial proliferation, and subepithelial cyclooxygenase 2 (COX-2) expression. Interestingly, a 5 time per week training for less than 60 min was not as protective against colon carcinogenesis as swimming for 90 min. This 90 min training indeed reduced serum cholesterol and triglycerides levels, as well as colonic lipid peroxidation in carcinogen-exposed rats. Our collective data suggest anticarcinogenic effects of physical exercises are potentially promoted when training 5 times a week for at least 60 min.