Inhibitory function of interferon on hepatocarcinogenesis.
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.


CONCLUSIONS
The data suggest potential clinical application of pegylated IFN for the prevention and treatment of hepatocellular carcinoma.
Yano
Hirohisa
H
Department of Pathology, Kurume University School of Medicine, Kurume, Japan. hiroyano@med.kurume-u.ac.jp
D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control*; D045744:Cell Line, Tumor; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000517:prevention & control*
D016588:Anticarcinogenic Agents; D007370:Interferon Type I