title: Enhancement of NK cells proliferation and function by Shikonin.
abstract: BACKGROUND
  Shikonin is a kind of naphthoquinone compound found mainly in Lithospermum erythrorhizon Sieb,et Zucc. Previous studies have shown that Shikonin has anti-tumor, anti-inflammatory and extensive pharmacological effects. According to new studies, Shikonin could also modulate the immune system function, but the effect to NK (nature killer) cells is yet unknown.
  
  
  OBJECTIVE
  To investigate the effect and mechanism of Shikonin on NK cells proliferation and cytotoxicity to colon cancer cell line (Caco-2).
  
  
  METHODS
  The proliferation and cytotoxicity of NK cells cultured with Shikonin were detected with CCK-8 assay. The expressions of perforin, GranB and IFN-γ were examined with FCM. The content of TNF-alpha was disclosed with ELISA kit. p-ERK1/2 and p-Akt expression of NK cells were detected with western blot.
  
  
  RESULTS
  With CCK-8 assay, it is found that Shikonin could significantly enhance NK cells proliferation and cytotoxicity to colon cancer cells. With FCM assay, it is found that Shikonin could improve the expression of perforin and GranB in a dose-dependent manner. Shikonin had no effect on TNF-alpha and IFN-γ expression. In mechanism, the study shows that Shikonin could enhance the expression of p-ERK1/2 and p-Akt.
  
  
  CONCLUSIONS
  Shikonin enhances NK cells proliferation and cytotoxicity via the improvement of perforin, GranB, p-ERK1/2 and p-Akt expression.
authors.affiliation: a Department of Oncology , The First Affiliated Hospital of Soochow University , Suzhou , P.R. China.|b Department of Oncology , The Affiliated Wujiang Hospital of Nantong University , Suzhou , P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: b Department of Oncology , The Affiliated Wujiang Hospital of Nantong University , Suzhou , P.R. China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Lu
authors.affiliation: c Central Laboratory, The Affiliated Wujiang Hospital of Nantong University , Suzhou , P.R. China.
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Gu
authors.affiliation: b Department of Oncology , The Affiliated Wujiang Hospital of Nantong University , Suzhou , P.R. China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ning
authors.affiliation: b Department of Oncology , The Affiliated Wujiang Hospital of Nantong University , Suzhou , P.R. China.
authors.forename: Tinghua
authors.initials: T
authors.lastname: Cao
authors.affiliation: b Department of Oncology , The Affiliated Wujiang Hospital of Nantong University , Suzhou , P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: b Department of Oncology , The Affiliated Wujiang Hospital of Nantong University , Suzhou , P.R. China.
authors.forename: Chengru
authors.initials: C
authors.lastname: Hu
authors.affiliation: a Department of Oncology , The First Affiliated Hospital of Soochow University , Suzhou , P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Tao
mesh_terms: D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007694:Killer Cells, Natural; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000276:immunology; D019950:Mitogen-Activated Protein Kinase 1 / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000276:immunology; D009285:Naphthoquinones / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology
chemical_list: D009285:Naphthoquinones; C016101:shikonin; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: NK cell; Shikonin; colon cancer cell; cytotoxicity; proliferation