A comparison of the antitumor effects of interferon-alpha and beta on human hepatocellular carcinoma cell lines.
The antiviral, antiproliferative and immunomodulatory effects of type I interferons (IFNs) are well documented, however, few studies have been published concerning differences in the antitumor effects of IFN-alpha and beta. In the present study, differences in antitumor effect, including the antiproliferative effect, cell cycle change, apoptosis, and the IFN-stimulated gene (ISG) were examined by flow cytometry between IFN-alpha and beta on three human hepatocellular carcinoma (HCC) cell lines (HepG2, Huh7 and JHH4). The antiproliferative effect of both IFNs on the HCC cell lines was time- and dose-dependent, and IFN-beta was significantly stronger than IFN-alpha. The cell cycle effect by both IFNs was an S-phase accumulation, with IFN-beta having a tendency to increase the S-phase ratio more strongly than IFN-alpha, especially in Huh7. Apoptosis marker expression, Fas antigen and intracellular active caspase-3, was increased after the addition of IFNs, especially of IFN-beta. The expression of human leukocyte antigen-class I molecules, ISG-encoded protein, was increased after the addition of IFNs, especially of IFN-beta. These data suggest that IFN-beta has a greater antitumor effect than IFN-alpha on HCC of a very early stage in patients with chronic hepatitis C.
Murata
Masayuki
M
Department of Environmental Medicine and Infectious Disease, Internal Medicine, Faculty of Medical Science Kyushu University, and Department of General Medicine, Kyushu University Hospital, Fukuoka, Japan.
Nabeshima
Shigeki
S
Kikuchi
Kensuke
K
Yamaji
Kouzaburo
K
Furusyo
Norihiro
N
Hayashi
Jun
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D019014:fas Receptor / Q000378:metabolism
D000970:Antineoplastic Agents; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; D019014:fas Receptor; D016899:Interferon-beta; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases