The up-regulation of type I interferon receptor gene plays a key role in hepatocellular carcinoma cells in the synergistic antiproliferative effect by 5-fluorouracil and interferon-α

  • Authors:
    • Shinji Oie
    • Mayumi Ono
    • Hirohisa Yano
    • Yuichiro Maruyama
    • Tadafumi Terada
    • Yuji Yamada
    • Takato Ueno
    • Masamichi Kojiro
    • Kazuyuki Hirano
    • Michihiko Kuwano
  • View Affiliations

  • Published online on: December 1, 2006     https://doi.org/10.3892/ijo.29.6.1469
  • Pages: 1469-1478
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Abstract

Combination therapy with interferon (IFN)-α and 5-fluorouracil (5-FU) has been reported to show an improved therapeutic efficacy in patients with advanced hepatocellular carcinoma (HCC) but the mechanism behind this has not been completely elucidated. We examined the molecular events underlying the antiproliferative effects of IFN-α and 5-FU in combination using six human HCC cell lines. When the antiproliferative effects of administering IFN-α and 5-FU together were analyzed using isobolograms, we found that the cell lines could be divided into two groups: the S-group containing three cell lines, which showed synergistic effects, and the A-group, containing the remaining three cell lines, which showed additive effects. Real-time RT-PCR and Western blot analyses revealed that the expression levels of type I IFN receptor subunits, IFNAR1 and IFNAR2, were specifically up-regulated by 5-FU in all three cell lines of the S-group with the exception of IFNAR2 in one cell line, but not in those of the A-group. IFN-α modulated the protein expression levels of six enzymes regulating sensitivity to 5-FU, but none of them were down- or up-regulated in the same way in all members of the S- or A-group. In conclusion, the 5-FU-induced modulation of IFN receptor expression could play a pivotal role in the therapeutic efficacy of IFN-α combined with 5-FU. Measuring the expression levels of IFN receptors, and their ability to be up-regulated, may be a promising method for selecting HCC patients for this type of combination therapy.

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December 2006
Volume 29 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Oie S, Ono M, Yano H, Maruyama Y, Terada T, Yamada Y, Ueno T, Kojiro M, Hirano K, Kuwano M, Kuwano M, et al: The up-regulation of type I interferon receptor gene plays a key role in hepatocellular carcinoma cells in the synergistic antiproliferative effect by 5-fluorouracil and interferon-α. Int J Oncol 29: 1469-1478, 2006
APA
Oie, S., Ono, M., Yano, H., Maruyama, Y., Terada, T., Yamada, Y. ... Kuwano, M. (2006). The up-regulation of type I interferon receptor gene plays a key role in hepatocellular carcinoma cells in the synergistic antiproliferative effect by 5-fluorouracil and interferon-α. International Journal of Oncology, 29, 1469-1478. https://doi.org/10.3892/ijo.29.6.1469
MLA
Oie, S., Ono, M., Yano, H., Maruyama, Y., Terada, T., Yamada, Y., Ueno, T., Kojiro, M., Hirano, K., Kuwano, M."The up-regulation of type I interferon receptor gene plays a key role in hepatocellular carcinoma cells in the synergistic antiproliferative effect by 5-fluorouracil and interferon-α". International Journal of Oncology 29.6 (2006): 1469-1478.
Chicago
Oie, S., Ono, M., Yano, H., Maruyama, Y., Terada, T., Yamada, Y., Ueno, T., Kojiro, M., Hirano, K., Kuwano, M."The up-regulation of type I interferon receptor gene plays a key role in hepatocellular carcinoma cells in the synergistic antiproliferative effect by 5-fluorouracil and interferon-α". International Journal of Oncology 29, no. 6 (2006): 1469-1478. https://doi.org/10.3892/ijo.29.6.1469