title: Vitamin K2 inhibits the growth of hepatocellular carcinoma via decrease of des-gamma-carboxy prothrombin.
abstract: BACKGROUND
  Des-gamma-carboxy prothrombin (DCP) is a serum protein produced by hepatocellular carcinoma (HCC) cells in the absence of vitamin K. Serum and tissue DCP expressions are thought to reflect the biological malignant potential of HCC. Hence, we aimed to examine the efficacy of vitamin K(2) on the production of DCP as well as tumor cell growth and invasion.
  
  
  METHODS
  Cell growth and viability were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The in vivo efficacy of vitamin K(2) was examined in nude mice bearing HCC cells. A 24-well transwell chamber was used to evaluate the motility and invasive ability of HCC cells. Levels of DCP in supernatant of cultures and in serum of mice were measured using an electrochemiluminescence immunoassay method. Western blot and immunohistochemical analysis were employed to evaluate the expression of DCP in HCC.
  
  
  RESULTS
  Vitamin K(2) (2-40 muM) significantly decreased the levels of DCP production in supernatant of PLC/PRF/5 and HepG2 cells and in serum of nude mice bearing HCC xenografts. The inhibition of DCP was also observed using the assays of Western blot analysis in HCC cultures and immunohistochemical analysis in HCC xenografts in mice. As a result of administration of vitamin K(2), the capacity of HCC growth was inhibited and the invasion and migration of tumor cells were decreased. Furthermore, the inhibitory effects of HCC growth were also observed in vivo and the sensitivity was well correlated with the decrease of DCP in the serum of mice.
  
  
  CONCLUSIONS
  Vitamin K(2) might suppress the growth and invasion of HCC cells via decrease of DCP.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Ma
authors.forename: Xian-Jun
authors.initials: XJ
authors.lastname: Qu
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Mu
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Chen
authors.forename: Yan-Na
authors.initials: YN
authors.lastname: Cheng
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kokudo
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Shu-Xiang
authors.initials: SX
authors.lastname: Cui
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008163:Luminescent Measurements; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D011498:Protein Precursors / Q000187:drug effects / Q000378:metabolism*; D011516:Prothrombin / Q000187:drug effects / Q000378:metabolism*; D024482:Vitamin K 2 / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D011498:Protein Precursors; D024482:Vitamin K 2; C008208:acarboxyprothrombin; D011516:Prothrombin