Journal
LIFE SCIENCES
Volume 83, Issue 23-24, Pages 815-820Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2008.10.003
Keywords
Des-gamma-carboxy prothrombin (DCP); Hepatocellular carcinoma cells (HCC); HepG2; SMMC-7721; Angiogenic factors
Funding
- National Natural Science Foundation of China [30672485]
- Shandong Provincial Foundation for Natural Science [Y2006C87]
- Ministry of Education, Science, Sports and Culture of Japan
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Aims: Des-gamma-carboxyl prothrombin (DCP) is a serum protein produced by hepatocellular carcinoma (HCC) cells. The aim of this study was to evaluate the angiogenic activity of DCP in HCC cells. Main methods: The proliferation of HCC cells was measured by 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The growth of HCC cells was also evaluated in vivo by using the xenografts in nude mice. The enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of angiogenic factors in supernatant of cell culture. The expression of angiogenic factors was examined. by Western blot analysis and immunohistochemical staining. Key findings: DCP displayed the stimulation of HCC cell growth in a dose (5-80 ng/ml) and time (24-96 h) dependent manner. The increase of cell growth was also observed in nude mice bearing well-established, palpable HepG2 and SMMC-7721 xenografts after 2 weeks administration of DCP. HCC cell growth was accompanied by the elevated levels of angiogenic factors. The levels of vascular endothelial growth factor (VEGF), transforming growth factor-alpha (TGF-alpha) and basic fibroblast growth factor (bFGF) in supernatant of SMMC-7721 cells were increased from 47, 126, and 60 pg/10(6) cells/24 h to 400, 208, and 298 pg/10(6) cells/24 h, respectively, after 72 h incubation with 80 ng/ml of DCP. The results of Western blot analysis and immunohistochemical staining of HCC xenografts also showed the significant increase of VEGF, TGF-alpha, and bFGF in HCC cells. Significance: These results provide the information that DCP is a type of growth factor in progression of HCC. (C) 2008 Published by Elsevier Inc.
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