The involvement of Th1 cell differentiation in the anti-tumor effect of purified polysaccharide from Sanghuangporus vaninii in colorectal cancer via multi-omics analysis

Abstract

Sanghuangporus vaninii is a medicinal mushroom, which has been used as a treatment for various diseases; however, the therapeutic potential and mechanism of action of S. vaninii in colorectal cancer (CRC) remain unknown. Herein, human colon adenocarcinoma cells were used to analyze the anti-CRC effects of the purified polysaccharide of S. vaninii (SVP-A-1) in vitro. In SVP-A-1-treated B6/JGpt-Apcem1Cin (Min)/Gpt male (ApcMin/+) mice, 16S rRNA sequencing was performed on cecal feces, metabolites were examined in serum, and LC-MS/MS protein detection was performed in colorectal tumors. Protein changes were further confirmed by various biochemical detection methods. Water-soluble SVP-A-1 with a molecular weight of 22.5 kDa was first obtained. SVP-A-1 prevented gut microbiota dysbiosis related to metabolic pathways of L-arginine biosynthesis, increased L-citrulline levels in the serum of ApcMin/+ mice, mediated L-arginine synthesis, and improved antigen presentation in dendritic cells and activated CD4+ T cells; the resulting Th1 cells released IFN-γ and TNF-α to act on tumor cells and promoted the sensitivity of tumor cells to cytotoxic T lymphocytes. In summary, SVP-A-1 exerted anti-CRC effects and has excellent potential for CRC treatment.