Vitamin D binding protein-macrophage activating factor inhibits HCC in SCID mice

J Surg Res. 2012 Jan;172(1):116-22. doi: 10.1016/j.jss.2010.07.057. Epub 2010 Sep 17.


Background: A high incidence of recurrence after treatment is the most serious problem in hepatocellular carcinoma (HCC). Therefore, a new strategy for the treatment of the disease is needed. The aim of the present study was to investigate whether vitamin D binding protein-macrophage activating factor (DBP-maf) is able to inhibit the growth of HCC.

Methods: The effects of DBP-maf on endothelial cells and macrophage were evaluated by WST-1 assay and phagocytosis assay, respectively. Human HCC cells (HepG2) were implanted into the dorsum of severe combined immunodeficiency (SCID) mice. These mice were divided into control and DBP-maf treatment groups (n = 10/group). The mice in the treatment group received 40 ng/kg/d of DBP-maf for 21 d.

Results: DBP-maf showed anti-proliferative activity against endothelial cells and also activated phagocytosis by macrophages. DBP-maf inhibited the growth of HCC cells (treatment group: 126 ± 18mm(3), untreated group: 1691.5 ± 546.9mm(3), P = 0.0077). Histologic examinations of the tumors revealed the microvessel density was reduced and more macrophage infiltration was demonstrated in the tumor of mice in the treatment group.

Conclusion: DBP-maf has at least two novel functions, namely, an anti-angiogenic activity and tumor killing activity through the activation of macrophages. DBP-maf may therefore represent a new strategy for the treatment of HCC.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology*
  • Macrophage-Activating Factors / pharmacology
  • Macrophage-Activating Factors / therapeutic use*
  • Macrophages / drug effects
  • Male
  • Mice
  • Mice, SCID
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / pathology
  • Phagocytosis / drug effects
  • Rats
  • Vitamin D-Binding Protein / pharmacology
  • Vitamin D-Binding Protein / therapeutic use*
  • Xenograft Model Antitumor Assays


  • Macrophage-Activating Factors
  • Vitamin D-Binding Protein
  • vitamin D-binding protein-macrophage activating factor