Polysaccharide Peptide Induced Colorectal Cancer Cells Apoptosis by Down-Regulating and Expression.

Background: Colorectal cancer (CRC) is the most frequent death-causing disease in the world. The mushroom, a traditional Chinese medicine, has been used as anti-cancer medicine with long history. Its cultured mycelia extracts, namely polysaccharide peptide (PSP) as the major active component in , is widely used in eastern countries to stimulate the immune system and treat deadly cancers, including CRC.

Methods: This study aimed to explore the mechanism through which PSP inhibits CRC cells proliferation. In vitro, cell proliferation and cytotoxicity of PSP were assessed using human CRC cell lines (HCT116 and HT29). The real-time polymerase chain reaction (PCR), western blot, and immunofluorescence methods were used to examine the expression of epidermal growth factor receptor (), programmed cell death-ligand 1 (), activator of transcription 3 (), , and in the PSP treated CRC cells. Human peripheral blood mononuclear cells (PBMC), which were activated with CD3/CD28/CD2 T cell activator and interleukin 2 (IL-2), were co-cultured with HCT116, which was pre-treated with PSP to reduce expression. The synergic effect of T-cells killing was evaluated using the terminal-deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) method.

Results: Polysaccharide peptide significantly inhibited proliferation of HCT116 and HT29 cell line in vitro. Polysaccharide peptide strongly reduced the expression and phosphorylation level of . In addition, PSP pretreatment significantly decreased the expression of downstream molecules and signaling pathways ( and ) in HCT116. Polysaccharide peptide pretreatment enhanced the T-cells killing effect induced by co-culture PBMC on HCT116 cells.

Conclusions: Polysaccharide peptide may be used as a prophylactic and therapeutic agent against CRC via down-regulating and signaling pathway.