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.
CONCLUSION: PEG-IFN-α2b in itself had remarkable anti-metastatic effects via inhibition of angiogenesis and cell adhesions.