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 alpha 2b (PEG-IFN-alpha 2b) 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-alpha 2b was subcutaneously administered into MH134 cells and tumor growth was evaluated. In distant metastasis models, PEG-IFN-alpha 2b 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-alpha 2b dosedependently. MH134 cells added with PEG-IFN-alpha 2b exhibited significantly lower levels of invasion potential. In vivo, tumor size in mice treated with PEG-IFN-alpha 2b 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-alpha 2b significantly suppressed angiogenesis compared with the control. Conclusion. PEG-IFN-alpha 2b in itself had remarkable anti-metastatic effects via inhibition of angiogenesis and cell adhesions. (C) 2012 Elsevier Inc. All rights reserved.