title: Toll-like receptor 4 mediates the antitumor host response induced by Ganoderma atrum polysaccharide.
abstract: The aim of this study is to investigate the role of Toll-like receptor (TLR) 4 in Ganoderma atrum polysaccharide (PSG-1)-induced antitumor activity. In vitro, the apoptosis rate of S-180 cells was increased in PSG-1-induced peritoneal macrophage derived from C3H/HeN (wild-type) mice, but not from C3H/HeJ (TLR4-deficient) mice. In the S-180 tumor model, phagocytosis, NO and ROS release, phosphorylation of MAPKs and Akt, and expression of NF-κB were increased by PSG-1 in peritoneal macrophage derived from C3H/HeN mice. Furthermore, PSG-1 elevated Th1 cytokine production and enhanced the cytotoxic activity of CTL and NK cells in C3H/HeN mice. In addition, PSG-1 decreased the tumor weight and increased the apoptosis rate and caspase-3 and caspase-9 activities of tumor derived from the C3H/HeN mice. However, none of these activities were observed in C3H/HeJ mice. In summary, these findings demonstrated that the antitumor activity of PSG-1 is mediated by TLR4.
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yu
authors.forename: Shao-Ping
authors.initials: SP
authors.lastname: Nie
authors.forename: Jun-Qiao
authors.initials: JQ
authors.lastname: Wang
authors.forename: Dan-Fei
authors.initials: DF
authors.lastname: Huang
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Li
authors.forename: Ming-Yong
authors.initials: MY
authors.lastname: Xie
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D032902:Ganoderma / Q000737:chemistry*; D006801:Humans; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D010587:Phagocytosis / Q000187:drug effects; D011134:Polysaccharides / Q000008:administration & dosage*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
chemical_list: D000970:Antineoplastic Agents; D011134:Polysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
keywords: Ganoderma atrum polysaccharide; Toll-like receptor 4; adaptive immunity; antitumor; innate immunity