title: Scorpion venom activates natural killer cells in hepatocellular carcinoma via the NKG2D-MICA pathway.
abstract: Previous studies have demonstrated that polypeptides extracted from scorpion venom (PESV) inhibited cell proliferation in several tumors, however, the effect on dysfunctional and exhausted natural killer cells which contribute to tumor escape from immune surveillance remain to be elucidated. In this study, we determined the effect of PESV on NK infiltration into H22 cells orthotopic transplantation tumors and on the expression of MHC class I chain-related proteins A (MICA) in HepG2 cells. We found that tumor growth in mice was significantly inhibited by PESV and the survival time of tumor-bearing mice treated with PESV was significantly prolonged. Moreover, levels of tumor-infiltrating NK cells, NKG2D protein, perforin and granzyme B mRNA were significantly increased in the group treated with PESV compared with the tumor-bearing control group. In addition, In addition, up-regulation of MICA by PESV enhances the susceptibility of HepG2 cells to NK lysis in vitro. These results indicate that the inhibitory effects of PESV on hepatic carcinoma are likely mediated by up-regulation of NK cell activity via the MICA-NKG2D pathway.
authors.affiliation: Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan 250062, China; School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan 250062, China.
authors.forename: Han
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Frontier Health Sciences, Tokyo Metropolitan University, 7-2-10 Higashiogu, Arakawa-ku, Tokyo, Japan.
authors.forename: Wang
authors.initials: W
authors.lastname: Zhidan
authors.affiliation: Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan 250062, China.
authors.forename: Ren
authors.initials: R
authors.lastname: Xia
authors.affiliation: Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan 250062, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Zhaoxia
authors.affiliation: Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan 250062, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Qing
authors.affiliation: Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan 250062, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Qiang
authors.affiliation: Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan 250062, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Haipeng
authors.affiliation: Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan 250062, China. Electronic address: wanghengxiao@aliyun.com.
authors.forename: Wang
authors.initials: W
authors.lastname: Hengxiao
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy*; D002465:Cell Movement / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000502:physiology; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D009368:Neoplasm Transplantation; D010455:Peptides / Q000627:therapeutic use*; D012604:Scorpion Venoms / Q000627:therapeutic use*; D012605:Scorpions / Q000276:immunology*; D019139:Tumor Escape / Q000187:drug effects
chemical_list: D015395:Histocompatibility Antigens Class I; C527086:Klrk1 protein, mouse; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K; D010455:Peptides; D012604:Scorpion Venoms
keywords: Hepatocellular carcinoma; MHC class I chain-related proteins A; Natural killer cells; Polypeptide; Receptor-natural killer group 2 member D; Scorpion venom