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Differential effects of interferon alpha-2b and beta on the signaling pathways in human liver cancer cells

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Abstract

Background

Interferon (IFN) has been reported to reduce the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C and the recurrence of HCC after effective treatment. We examined the effect of IFNs on the proliferation and the signaling pathways of human HCC cells.

Methods

Cellular proliferation was examined by a modified 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. Activities of signaling molecules were evaluated by Western blot analysis.

Results

Cellular growth was not significantly modulated by IFNα-2b or by IFN-β, even though the HCC cells expressed the IFN receptors. However, extracellular signal-regulated kinase (ERK)1/2 was activated by treatment with IFNα-2b, and both ERK1/2 and AKT were activated by treatment with IFN-β, implying a possible role in resistance to IFNs. Contrary to our expectations, inhibition of mitogen-activated ERK-regulating kinase (MEK) or phosphatidylinositol-3-OH kinase (PI3K) did not modulate the proliferation of HCC cells. Also, abrogation of the ERK1/2 and AKT signaling pathways did not affect cell-cycle arrest at the G1/S phase caused by IFNα-2b.

Conclusions

IFNα-2b and IFN-β activated ERK1/2 and/or AKT independently of modulating the proliferation of HCC cells and the cell-cycle machinery. A signal transduction-based approach for HCC treatment needs to focus on other possible signaling molecules besides ERK1/2 and AKT when challenged with IFNs.

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Authors and Affiliations

  1. Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, 683-8504, Japan

    Kazuya Matsumoto, Jun-ichi Okano & Yoshikazu Murawaki

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  1. Kazuya Matsumoto
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  2. Jun-ichi Okano
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  3. Yoshikazu Murawaki
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Matsumoto, K., Okano, Ji. & Murawaki, Y. Differential effects of interferon alpha-2b and beta on the signaling pathways in human liver cancer cells. J Gastroenterol 40, 722–732 (2005). https://doi.org/10.1007/s00535-005-1616-x

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  • DOI: https://doi.org/10.1007/s00535-005-1616-x

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