Pegylated Interferon-α2a Inhibits Proliferation of Human Liver Cancer Cells In Vitro and In Vivo

Purpose: We investigated the effects of pegylated interferon-alpha 2a (PEG-IFN-alpha 2a) on the growth of human liver cancer cells. Methods: The effect of PEG-IFN-alpha 2a on the proliferation of 13 liver cancer cell lines was investigated in vitro. Cells were cultured with medium containing 0-4,194 ng/mL of PEG-IFN-alpha 2a, and after 1, 2, 3, or 4 days of culture, morphologic observation and growth assay were performed. After hepatocellular carcinoma (HCC) cells (HAK-1B and KIM-1) were transplanted into nude mice, various doses of PEG-IFN-alpha 2a were subcutaneously administered to the mice once a week for 2 weeks, and tumor volume, weight, and histology were examined. Results: PEG-IFN-alpha 2a inhibited the growth of 8 and 11 cell lines in a time-and dose-dependent manner, respectively, although the 50% growth inhibitory concentrations of 7 measurable cell lines on Day 4 were relatively high and ranged from 253 ng/mL to 4,431 ng/mL. Various levels of apoptosis induction were confirmed in 8 cell lines. PEG-IFN-alpha 2a induced a dose-dependent decrease in tumor volume and weight, and a significant increase of apoptotic cells in the tumor. Subcutaneous administration of clinical dose for chronic hepatitis C (3 mu g/kg, 0.06 mu g/ mouse) was effective and induced about 30-50% reduction in the tumor volume and weight as compared with the control. Conclusions: Although in vitro anti-proliferative effects of PEG-IFN-alpha 2a were relatively weak, PEG-IFN-alpha 2a induced strong anti-tumor effects on HCC cells in vivo. The data suggest potential clinical application of PEG-IFN-alpha 2a for the prevention and treatment of HCC.