Polygonatum sibiricum polysaccharides play anti-cancer effect through TLR4-MAPK/NF-κB signaling pathways

Abstract

Objective: To investigate the anti-cancer effect of Polygonatum sibiricum polysaccharides (PSP) and the underlying mechanism.

Methods: Tumor-bearing mice were randomly divided into normal saline (NS) group, adriamycin (ADM) group, PSP group and lipopolysaccharide (LPS) group. RAW264.7 cells were pre-treated with or without TLR4 inhibitor or MyD88 inhibitor. Quantitative RT-PCR and Western blot were performed to detect the mRNA and protein expressions, respectively. ELISA and Griess reaction was used to measure cytokines and NO levels. Flow cytometry was employed to examine T-lymphocyte subset and CCK-8 assay was used for cell viability.

Results: The in vivo experiment found that PSP inhibited tumor growth and improved the spleen index, thymus index, the cytokines secretion and CD4⁺/CD8⁺ lymphocytes ratio. Compared with the NS group, the mRNA and protein expressions of the critical nodes inTLR4-MAPK/NF-κB signaling pathways (except TRAM) significantly increased in PSP group, as well as the NO and cytokines levels. Nevertheless, PSP had no obvious effects on TRAM. Further analysis showed that PSP effects on the critical nodes in TLR4-MAPK/NF-κB signaling pathways were suppressed by inhibitor in vitro.

Conclusion: The immunoenhancement effect of PSP against lung cancer is mediated by TLR4-MAPK/NF-κB signaling pathways.

Keywords: Immuneregulation; Lung cancer; Polygonatum sibiricum polysaccharides (PSP); TLR4.