Immunoregulatory function and anticancer effects of Polygonatum sibiricum polysaccharides against hepatic carcinoma via macrophage phenotype modulation.

Polysaccharides extracted from traditional Chinese medicine are biological macromolecules and the main compounds responsible for immunoregulatory effects. The immunoregulatory properties and anticancer effects of Polygonatum sibiricum polysaccharide (PSP) were found to be attributed to modulation of the phenotype of tumor-associated macrophages (TAMs). The underlying molecular mechanisms were elucidated. PSP is a natural macromolecule consisting of different functional groups. In vitro findings suggested the immunoregulatory function of PSP and that it could transform the M2 phenotype of macrophages toward the M1 phenotype. Studies at the molecular level revealed that the immunoregulatory and macrophage phenotype-modulatory functions of PSP were mediated by the TLR4-mediated MyD88-dependent signaling pathway. In vivo, PSP exhibited a strong tumor-inhibitory effect on hepatic carcinoma, and PSP-treated tumor-bearing mice exhibited a lower tumor cell-proliferation index as determined using immunohistochemical assays. PSP could increase the number of CD86-positive TAMs and decrease the number of CD206-positive TAMs in tumor tissues as determined using immunofluorescence assays. PSP exerted its immunoregulatory and anticancer effects by modulating the phenotype of TAMs toward the M1 phenotype via the TLR4-mediated MyD88-dependent signaling pathway. Our findings provide a potential strategy for the treatment of hepatic carcinoma.