Des-Gamma-Carboxy Prothrombin Increases The Expression Of Angiogenic Factors In Human Hepatocellular Carcinoma Cells

Des-γ-carboxyl prothrombin(DCP) is a serum protein produced by hepatocellular carcinoma(HCC) cells.Serum and tissue DCP expressions are thought to reflect the biological malignant potential of HCC.In this study,we evaluated the angiogenic activity of DCP in human hepatocellular carcinoma cells.DCP displayed stimulation of HCC cell growth in a dose- and time- dependent manner in vitro as measured by 3-[4,5-dimethylthiazol-2-yl]- 2,5-diphenyltetrazolium bromide(MTT) assays.HCC cell growth was accompanied by the elevated levels of angiogenic factors evaluated using Western blotting analysis.The expressions of vascular endothelial growth factor(VEGF),transforming growth factor-alpha(TGF-α) and beta fibroblast growth factor(bFGF) in HepG-2 and SMMC-7721 cells were increased after 48 h incubation with DCP.The increase of HCC cell growth was confirmed in the immunodeficient mice bearing well-established,palpable HepG-2 and SMMC-7721 xenografts after 2 weeks administration of DCP.We further examined the expressions of angiogenic factors in HCC xenografts using immunohistochemical analysis methods.The results revealed a significant dose-dependent increase of VEGF, TGF-α,and bFGF expressions in cancer cells.Angiogenesis in hepatoma xenografts was also increased as assessed by microvessel count(MVD).These results demonstrate that DCP stimulates the growth of human hepatocellular carcinoma cells accompanied by the increase of angiogenic factors expression in cancer cells.