title: The anti-lung cancer activity of SEP is mediated by the activation and cytotoxicity of NK cells via TLR2/4 in vivo.
abstract: Strongylocentrotus nudus egg polysaccharide (SEP) has been reported to display antitumor activity. However, the effects of SEP and its underlying mechanism in the treatment of lung cancer remain unclear, particularly with an immunodeficient mouse model of human non-small cell lung cancer (NSCLC). In the present study, we investigated the anti-lung cancer effects of SEP and its underlying mechanism of action in both Lewis lung cancer (LLC)-bearing C57/BL6J mice and human NSCLC H460-bearing nude mice. Although SEP showed no inhibitory effects on tumor cells in vitro, it markedly stimulated the percentage of CD3-NK1.1(+) cells and natural killer (NK) cell cytotoxicity in the spleens of nude mice and C57/BL6J mice. In LLC-bearing mice, SEP not only inhibited tumor growth but also promoted NK-mediated cytotoxicity, the NK1.1(+) cell population, and IL-2 and IFN-γ secretion. SEP significantly suppressed H460 growth in nude mice, which was abrogated by the selective depletion of NK cells via the intraperitoneal injection of anti-asialo GM-1 antibodies. Furthermore, anti-TLR2/4 antibodies blocked both SEP and NK cell binding and SEP-induced perforin secretion. SEP-induced proliferation and IFN-γ secretion by NK cells in wild type mice were partially impaired in TLR2 or TLR4 knockout mice. These results suggest that SEP-promoted NK cytotoxicity, which was partially mediated via TLR2 and TLR4, was the main contributing factor to lung cancer inhibition in vivo and that SEP may be a potential immunotherapy candidate for the treatment of lung cancer.
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Mengyun
authors.initials: M
authors.lastname: Ke
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Dou
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xi
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China. Electronic address: cl_zhou@cpu.edu.cn.
authors.forename: Changlin
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001483:Base Sequence; D018827:Carcinoma, Lewis Lung / Q000473:pathology*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D011134:Polysaccharides / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047269:Strongylocentrotus / Q000737:chemistry; D051195:Toll-Like Receptor 2 / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*
chemical_list: D017931:DNA Primers; D011134:Polysaccharides; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
keywords: Immunotherapy; Lung cancer; Natural killer cell; SEP; TLR