Lactobacillus fermentum ZS09 Mediates Epithelial– Mesenchymal Transition (EMT) by Regulating the Transcriptional Activity of the Wnt/β-Catenin Signalling Pathway to Inhibit Colon Cancer Activity

Abstract

Objective: The epithelial–mesenchymal transition (EMT) pathway can mediate tumour migration, and the occurrence of EMT is closely related to the Wnt/β-catenin signalling pathway. The purpose of this paper was to study the effect of Lactobacillus fermentum ZS09 (L. fermentum ZS09) on the EMT pathway in mouse with azoxymethane/dextran sulfate sodium salt (AOM/DSS) induced colon cancer and the potential underlying mechanism. Materials and Methods: In this study, a mouse colon cancer model was established through intraperitoneal injection of 10 mg/kg azoxymethane (AOM) and three cycles of 2.5% dextran sulfate sodium salt (DSS) in the drinking water. H&E staining, enzyme-linked immunosorbent assay (ELISA), real-time fluorescent quantitative PCR (RT-qPCR) and Western blotting (WB) were used to study the antitumour mechanisms of L. fermentum ZS09 through the EMT pathway. Results: The results of this study showed that compared with the model group, the high-dose L. fermentum ZS09 intervention group exhibited decreased serum levels of MMP-9, TNF-α, IL-6R, Ang-2 and VEGFR-2 and increased contents of DKK1 (P<0.05). The expression of Wnt/β-catenin signalling pathway-related genes (Dv1, GSK-3β, β-catenin, c-myc, cyclinD1, Vim, and MMP-9) was significantly reduced, and the gene expression levels of APC, CDH1, and Axin were increased. The levels of related proteins (β-catenin, N-cadherin, and VEGF) were downregulated, and the levels of p-β-catenin and E-cadherin were upregulated. Conclusion: The results indicate that L. fermentum ZS09 could inhibit EMT and angiogen-esis pathways by inhibiting the Wnt/β-catenin signalling pathway, which could inhibit tumour metastasis.