<i>Lactobacillus plantarum</i> SMUM211204 Exopolysaccharides Have Tumor-Suppressive Effects on Colorectal Cancer by Regulating Autophagy via the mTOR Pathway

Probiotics have demonstrated their ability to suppress tumors in cell lines and mouse models. However, the precise molecules responsible for these effects remain unidentified. We focused on isolating and analyzing the exopolysaccharides (EPSs) produced by <i>Lactobacillus plantarum</i> (<i>L. plantarum</i>) SMUM211204. Our findings confirm that EPSs impair the growth of HCT116 cells and induce autophagy and apoptosis. Moreover, further experimental evidence demonstrates that EPSs diminish the expression of phosphorylation levels of PI3K, AKT, and mTOR. In contrast, they boost the expression of AMPKa, elevate the ULK1 level, and increase the protein LC3-II/I ratio. Furthermore, when rapamycin is employed to impede EPS-induced autophagy, it results in an enhancement of apoptosis and cell death in HCT116 cells. To validate these findings <i>in vivo</i>, we conducted an animal study using a colorectal cancer xenograft model. The results showed a significant reduction in tumor volume and weight in the EPS-treated group compared with the control group. Immunohistochemical analysis of tumors indicated increased expressions of LC3 and caspase-3, along with decreased levels of phospho-PI3Kinase, phospho-AKT, and P62, consistent with <i>in vitro</i> findings. Our study proved that EPSs have an inhibitory effect on colorectal cancer and can be used as a preventive and therapeutic drug for cancer.