Growth inhibitory effects of pegylated IFN α‐2b on human liver cancer cells in vitro and in vivo

Abstract: Purpose: We investigated the effects of pegylated IFN‐α2b (PEG‐IFN‐α2b) on the growth of human liver cancer cells.Methods: The effect of PEG‐IFN‐α2b on the proliferation of 13 liver cancer cell lines was investigated in vitro. Chronological changes in growth and IFN‐α receptor‐2 (IFNAR‐2) expression were monitored in hepatocellular carcinoma (HCC) cells (HAK‐1B) cultured with PEG‐IFN‐α2b. After HAK‐1B cells were transplanted into nude mice, various doses of PEG‐IFN‐α2b or IFN‐α2b were administered, and tumor volume, weight, histology, and IFNAR‐2 expression were examined.Results: PEG‐IFN‐α2b inhibited the growth of nine cell lines with apoptosis in a dose‐ and time‐dependent manner. Continuous contact with PEG‐IFN‐α2b induced time‐dependent growth inhibition and down‐regulation of IFNAR‐2 expression. PEG‐IFN‐α2b 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‐α2b was significantly stronger than that of non‐PEG‐IFN‐α2b in vivo.Conclusions: Continuous contact with PEG‐IFN‐α2b induces strong antitumor effects and the down‐regulation of IFNAR‐2 in HCC cells. The data suggest potential clinical application of PEG‐IFN‐α2b for the prevention and treatment of HCC.