Lacticaseibacillus paracasei - derived extracellular vesicles inhibits colorectal cancer growth via decreasing HIF-1α-mediated glycolysis

Colorectal cancer is one of the most common malignant cancers worldwide. Since colon cancer cells rely on glycolysis as their major energy source, glycolytic metabolism has become a major problem for colon cancer therapy. Lacticaseibacillus paracasei has anti-colon cancer effects, and its secreted extracellular vesicles involved in intercellular communication can induce colon cancer cell apoptosis, but the effect on glycolytic metabolism remains enigmatic. Our findings demonstrate that LpEVs were ingested in by colorectal cancer and prevent the proliferation of colon cancer cells. LpEVs treatment altered the expression of glycolysis-related genes in colon cancer cells, and the differentially expressed genes were highly enriched in the HIF-1 signaling pathway. Experimental analysis further suggested that, LpEVs reduced the expression of HIF-1, GLUT4, and LDHA, which hindered the glycolysis of colorectal cancer cells. Consequently, LpEVs decreased colon cancer cell glucose uptake rate, lactate generation, and LDH activity. In vivo , LpEVs inhibited the growth of CRC xenograft in nude mice and the expression of HIF-1α, GLUT4 and LDHA. Overall, we reveal that LpEVs exert its anti-colon cancer activity via decreasing HIF-1α-mediated glycolysis. We hypothesized that our research would provide a theoretical framework for creating innovative CRC therapeutic approaches.