Vitamin K2 Inhibits The Growth Of Hepatocellular Carcinoma Cells Via Decreasing The Expression Of Des-gamma-carboxy Prothrombin (DCP)

Background:Des-γ-carboxyl 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 K2 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(MTT) assay.The in vivo efficacy of vitamin K2 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 the electrochemiluminescence immunoassay method.Western blot and immunohistochemical analysis were employed to evaluate the expression of DCP in HCC cells.Results:Vitamin K2(2-40μM) significantly decreased the levels of DCP production in supernatant of PLC/PRF/5 and HepG-2 cells cultures and in serum of nude mice bearing HCC xenografts.Inhibition of DCP expression 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 K2,the capacity of HCC cells growth was inhibited and the invasion and migration of tumor cells were decreased.Furthermore,the inhibitory effects of HCC cells growth were also observed in vivo and the sensitivity was well correlated with the declines of DCP levels in serum of mice.Conclusion:Vitamin K2 might suppress the growth and invasion of hepatocellular carcinoma cells via decreasing the expression of DCP.