Effects of pegylated interferon α2b on metastasis of hepatocellular carcinoma.
OBJECTIVE
Interferon (IFN) has an anti-tumor activity in hepatocellular carcinoma (HCC) via anti-angiogenesis and induction of apoptosis. We have previously reported anti-metastatic effects of IFN combined chemotherapy on the outcome of HCC patients. The aim of this study was to investigate anti-metastatic effects of IFN.


METHODS
In vitro, pegylated interferon α2b (PEG-IFN-α2b) was administered to mouse MH134 cells (mouse HCC cell line, MH134), and anti-implantation effects were examined by evaluating the inhibition of cell invasion and cell proliferation. Expressions of vascular endothelial growth factor (VEGF) mRNA were also measured. In vivo, PEG-IFN-α2b was subcutaneously administered into MH134 cells and tumor growth was evaluated. In distant metastasis models, PEG-IFN-α2b was subcutaneously administered and MH134 cells were injected into the spleen. The number of liver metastases and microvessel densities (MVD) were counted.


RESULTS
In vitro, the proliferation of MH134 cells was significantly suppressed by PEG-IFN-α2b dose-dependently. MH134 cells added with PEG-IFN-α2b exhibited significantly lower levels of invasion potential. In vivo, tumor size in mice treated with PEG-IFN-α2b significantly suppressed compared with control mice (mean 0.5 versus 5.0 cm, in diameter, P < 0.05) and also decreased number of liver metastases (19.3 versus 6.0, P < 0.05). Moreover, PEG-IFN-α2b significantly suppressed angiogenesis compared with the control.


CONCLUSIONS
PEG-IFN-α2b in itself had remarkable anti-metastatic effects via inhibition of angiogenesis and cell adhesions.
Arakawa
Yusuke
Y
Department of Surgery, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
Shimada
Mitsuo
M
Utsunomiya
Tohru
T
Imura
Satoru
S
Morine
Yuji
Y
Ikemoto
Tetsuya
T
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b