Plantaricin BM-1 enhances anti-colorectal cancer effects by inhibiting CD8+ cytotoxic T cell apoptosis via the ERK/AP1/Bim signaling pathway.

Abstract

INTRODUCTION: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality. Plantaricin BM-1, a class IIa bacteriocin from Lactobacillus plantarum, exhibits anticancer potential, but itsefficacy against CRC is unclear. METHODS: Using an AOM/DSS-induced CRC mouse model, we administered Plantaricin BM-1 orally and evaluated therapeutic effects via phenotypic, pathological, and inflammatory assessments. scRNA-seq elucidated molecular mechanisms, validated by RT-qPCR, IHC, flow cytometry, and Western blot. DISCUSSION: ResultsResults demonstrated that Plantaricin BM-1 significantly suppressed tumorigenesis, colon shortening, serum TNF-α levels, and pathological damage. scRNA-seq revealed a 17.38% increase in tumor-infiltrating T cells and a 9.29% expansion of cytotoxic CD8⁺ T cells. Key cytotoxic genes (Gzma, Gzmb, Fasl) were upregulated in CD8⁺ T cells, while the ERK/AP1 pathway was suppressed. Consistently, Plantaricin BM-1 downregulated ERK, AP1, and pro-apoptotic Bimand. Crucially, it inhibited CD8⁺ T cell apoptosis via the ERK/AP1 pathway. DISCUSSION: These findings provide mechanistic insights for developing Plantaricin BM-1 as an anti-CRC agent.