Clinical Studies: Growth inhibitory effects of pegylated IFN a-2b on human liver cancer cells in vitro and in vivo

We investigated the effects of pegylated IFN-a2b (PEG-IFN-a2b) on the growth of human liver cancer cells. Methods: The effect of PEG-IFN-a2b on the proliferation of 13 liver cancer cell lines was investigated in vitro. Chronological changes in growth and IFN-a receptor-2 (IFNAR-2) expression were monitored in hepatocellular carcinoma (HCC) cells (HAK-1B) cultured with PEG-IFN-a2b. After HAK-1B cells were transplanted into nude mice, various doses of PEG-IFN-a2b or IFN-a2b were administered, and tumor volume, weight, histology, and IFNAR-2 expression were examined. Results: PEG-IFN-a2b inhibited the growth of nine cell lines with apoptosis in a dose- and time-dependent manner. Continuous contact with PEG-IFN-a2b induced time-dependent growth inhibition and down-regulation of IFNAR-2 expression. PEG-IFN-a2b induced a dose-dependent decrease in tumor volume and weight, a significant increase of apoptotic cells, and a decrease in IFNAR-2 expression in the tumor. The clinical dose for chronic hepatitis C was also effective. The antitumor effect of PEG-IFN-a2b was significantly stronger than that of non-PEG-IFN-a2b in vivo. Conclusions: Continuous contact with PEG-IFN-a2b induces strong antitumor effects and the down-regulation of IFNAR-2 in HCC cells. The data suggest potential clinical application of PEG-IFN-a2b for the prevention and treatment of HCC.