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

Jia Liu; Xiufeng Chen; Xianrong Zhou; Ruokun Yi; Zhennai Yang; Xin Zhao

doi:10.2147/JIR.S344564

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

J Inflamm Res. 2021 Dec 22:14:7281-7293. doi: 10.2147/JIR.S344564. eCollection 2021.

Authors

Jia Liu^#¹, Xiufeng Chen^#², Xianrong Zhou¹, Ruokun Yi¹, Zhennai Yang³, Xin Zhao¹

Affiliations

¹ Chongqing Collaborative Innovation Center for Functional Food, Chongqing Engineering Research Center of Functional Food, Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing, 400067, People's Republic of China.
² Gastrointestinal Cancer Center, Chongqing University Cancer Hospital, Chongqing, 400044, People's Republic of China.
³ Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology & Business University (BTBU), Beijing, 100048, People's Republic of China.

^# Contributed equally.

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 angiogenesis pathways by inhibiting the Wnt/β-catenin signalling pathway, which could inhibit tumour metastasis.

Keywords: EMT pathway; Lactobacillus fermentum ZS09; Wnt/β-catenin signalling pathway; colon cancer.

Grants and funding

This research was funded by the Chongqing University Innovation Research Group Project (CXQTP20033), the Science and Technology Project of the Chongqing Education Commission (KJZD-K202001602) General Program of Natural Science Foundation of Chongqing (cstc2021jcyjmsxmX0070), and the Research Project of Chongqing University of Education (KY201920C), China.