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Study of the effects of interferon a on several human hepatoma cell lines: analysis of the signalling pathway of the cytokine and of its effects on apoptosis and cell proliferation
Author(s) -
Legrand A.,
Vadrot N.,
Lardeux B.,
Bringuier A.F.,
Guillot R.,
Feldmann G.
Publication year - 2004
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2004.00899.x
Subject(s) - stat protein , apoptosis , irf1 , cell growth , signal transduction , interferon , cytokine , biology , microbiology and biotechnology , suppressor of cytokine signalling , transcription factor , cell , cancer research , stat3 , socs3 , immunology , biochemistry , gene
Background: Interferon α (IFNα), currently used for the treatment of chronic viral hepatitis, is also known to prevent the development of hepatocellular carcinoma (HCC), the mechanism of this action being still debatable. Aims: To study thoroughly in human hepatoma cell lines (HHL) – Hep3B, HepG2, HuH7, SKHep1, and Chang‐Liver – submitted to rhIFNα, the signalling pathway of IFNα, the binding activity of the cytokine on specific gamma‐activated sequence (GAS) and interferon‐stimulated regulatory element (ISRE) nuclear sequences, and its effects on apoptosis and cell proliferation. Methods: The behaviour of signal transducer and activator of transcription (STAT)1, STAT2, p48 IRF9 and the binding of nuclear proteins were investigated by immunoblot and electro‐mobility shift assay. Expression of some IFNα‐dependent proteins – p21/ WAF1 , inducible nitric oxide synthase, IRF1 and 2 – were studied by immunoblot. Apoptosis and the cell cycle were studied by morphological and biochemical methods. Results: Transduction of INFα was unaltered, although there were some variations in the different HHL. Nuclear protein binding to GAS or ISRE showed that ISRE was mainly involved. Apoptosis did not occur. The cell cycle was slightly modified in HuH7. Three GAS‐ and/or ISRE‐dependent proteins increased, suggesting that IFNα may have some biological effects on HHL. Conclusions: The IFNα signalling pathway is functional in several HHL, but the cytokine has no apoptotic effect and a moderate anti‐proliferative effect. This suggests that the preventive role of IFNα on HCC cannot be explained by an apoptotic and/or an anti‐proliferative effect, but possibly by its action on several specific nuclear sequences that protect liver cells from transformation.