Immunomodulatory effect of Ganoderma atrum polysaccharide on CT26 tumor-bearing mice

Ganoderma atrum has attracted great attention for its antitumor activity. However, the mechanism remains unclear. A G. atrum polysaccharide (PSG-1) showed pronounced antitumor activity in this study. PSG-1 did not kill CT26 cells directly, but inhibited the proliferation of CT26 cells via the activation of peritoneal macrophages (MΦ). In vivo, PSG-1 significantly suppressed the tumor growth in CT26 tumor-bearing mice. The treatment caused a significant increase in the immune organ index and the phagocytosis of macrophages. The production of TNF-α, IL-1β and nitric oxide also increased. Furthermore, we found that PSG-1 acted on Toll-like receptor (TLR) 4, signaled through p38 MAPK pathway, then activated NF-κB and stimulated TNF-α production. We further found that PSG-1 increased the expression of TLR4 and NF-κB, the degradation of IκBα and the phosphorylation of p38 MAPK. In summary, we have demonstrated that PSG-1 could activate macrophages via TLR4-dependent signaling pathways, improve immunity and inhibit tumor growth.