Inhibitory function of interferon on hepatocarcinogenesis
1Department of Pathology, Kurume University School of Medicine, Kurume, Japan. hiroyano@med.kurume-u.ac.jp
Objective:
We examined the growth-inhibitory effect and the mechanism of action of type I interferon (IFN) in human liver cancer cell lines in vitro and in vivo.
Methods:
We examined the growth-inhibitory effect of 5 types of type I IFN preparations (e.g., pegylated, nonpegylated IFN-alpha, and IFN-beta) used for the treatment of chronic hepatitis C in 13 liver cancer cell lines in vitro. After liver cancer cells were transplanted into nude mice, various doses of IFN preparations were subcutaneously administered, and the antitumor effect was examined.
Results:
The growth-inhibitory effect of each preparation was different, but IFN-beta expressed the strongest effects in vitro. Induction of an inhibition of cell cycle progression at the G(1), S or G(2)/M phase with or without apoptosis was the mechanism of action of IFN. IFN preparations induced a dose-dependent decrease in tumor volume and weight by inducing tumor cell apoptosis in vivo, and tumor growth was effectively suppressed even at the clinical dose for chronic hepatitis C treatment. The antitumor effect of pegylated IFN was significantly stronger than that of nonpegylated IFN.
Conclusion:
The data suggest potential clinical application of pegylated IFN for the prevention and treatment of hepatocellular carcinoma.
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