Lactobacillus species inhibitory effect on colorectal cancer progression through modulating the Wnt/ß-catenin signaling pathway.

ABSTRACT

Probiotic bacteria are known to exert a wide range of anticancer activities on their animal hosts. In the present study, the anticancer effect of a cocktail of several potential probiotic Lactobacillus species (potential probiotic L.C) was investigated in vitro and in vivo. MTT and Flow cytometry tests results showed that administration of live potential probiotic L.C significantly decreased the HT-29 and CT-26 cells proliferation and induced late apoptotis in a time-dependent manner. In addition, quantitative real-time polymerase chain reaction (qPCR) results showed that exposure of potential probiotic L.C to both HT-29 and CT-26 cells during the incubation times resulted in the upregulation (apc and CSNK1ε for HT-29, CSNK1ε and gsk3ß for CT-26) and downregulation (CTNNB1, CCND1, pygo2, axin2 and id2) of the Wnt/ß- catenin pathway-related genes in a time-dependent manner. The significance of in vitro anticancer effect of potential probiotic L.C was further confirmed in an experimental tumor model. Data from the murine model of colorectal cancer (CRC) induced by Azoxymethane (AOM) and Dextran Sulfate Sodium (DSS) showed significantly alleviated inflammation and tumor development in AOM/DSS/L.C-injected mice compared to the AOM/DSS-injected mice. Tumor growth inhibition was accompanied by potential probiotic L.C-driven upregulation and downregulation of the Wnt/ß-catenin pathway-related genes, similar to the in vitro results. These results showed that potential probiotic L.C inhibited the tumor growth, and that its anticancer activity was at least partially mediated through suppressing the Wnt/ß-catenin pathway. Overall, the present study suggested that this probiotic could be used clinically as a supplement for CRC prevention and treatment.