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


CONCLUSIONS
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.
Nonaka
Koichi
K
Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan. kknonaka@mbn.nifty.com
Onizuka
Shinya
S
Ishibashi
Hiromi
H
Uto
Yoshihiro
Y
Hori
Hitoshi
H
Nakayama
Toshiyuki
T
Matsuura
Nariaki
N
Kanematsu
Takashi
T
Fujioka
Hikaru
H
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016215:Macrophage-Activating Factors / Q000494:pharmacology / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D014809:Vitamin D-Binding Protein / Q000494:pharmacology / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
D016215:Macrophage-Activating Factors; D014809:Vitamin D-Binding Protein; C101908:vitamin D-binding protein-macrophage activating factor