Probiotic supplementation attenuates the aggressiveness of chemically induced colorectal tumor in rats

Abstract

To evaluate the effect of a probiotic on the aggressiveness of a chemically induced colorectal tumor in rats. Twenty-five male Fisher 344 rats, 250 g, provided with feed and water ad libitum, were randomly divided into 5 groups (5 rats/group): G_Control, no treatment; G_Tumor, tumor induction; G_Tumor+5FU, tumor induction, 5-Fluorouracil applied; G_Tumor+Prob, induction of the tumor, supplemented with probiotic; G_{Tumor+5-FU+Prob}, tumor induction, 5-Fluorouracil applied, supplemented with probiotic. For tumor induction 20 mg/kg of 1,2-dimethylhydrazine was applied intraperitoneally over 4 weeks, followed by an interval of 15 days, and then repeated for a further 4 weeks. Five weeks after the final dose of the carcinogen, treatment was initiated with 5-Fluorouracil (15 mg/kg, intraperitoneally/week) and a commercial probiotic (1 × 10⁹ CFU, daily/gavage). Data were analyzed by One Way Variance Analysis and means compared by Dunnett's test. GraphPad Prism statistical software was used. The histopathological analyzes were evaluated by the chi-square test. A 5% type-I error was considered statistically significant. Compared with the G_Tumor, the G_Tumor+Prob (p < 0.0373) and G_{Tumor+5-FU+Prob} (p < 0.0003) demonstrated an attenuated effect on the aggressiveness of the colorectal tumor, with a reduction in the count of Aberrant Crypt foci; and a lower percentage of malignant neoplastic lesions in the G_Tumor+Prob (40% low grade tubular adenoma, 40% carcinoma in situ, 20% low grade adenocarcinoma) and G_{Tumor+5-FU+Prob} (40% low grade tubular adenoma and 60% carcinoma in situ). Probiotic supplementation has the potential to decrease the formation of aberrant crypts and ameliorate tumor malignancy, enhancing the antitumor effect of 5-Fluorouracil chemotherapy in colic segments.

Keywords: Aberrant crypt foci; Chemotherapy; Colorectal cancer; Functional food; Intestinal microbita.