Vitamin K2 inhibits the growth of hepatocellular carcinoma via decrease of des-gamma-carboxy prothrombin.
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.
Ma
Meng
M
Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan, China.
Qu
Xian-Jun
XJ
Mu
Guo-Ying
GY
Chen
Ming-Hui
MH
Cheng
Yan-Na
YN
Kokudo
Norihiro
N
Tang
Wei
W
Cui
Shu-Xiang
SX
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*
D015415:Biomarkers; D011498:Protein Precursors; D024482:Vitamin K 2; C008208:acarboxyprothrombin; D011516:Prothrombin