Cancer Immunology, Immunotherapy

, Volume 58, Issue 12, pp 2031–2037

Bortezomib pre-treatment prolongs interferon-alpha-induced STAT1 phosphorylation in melanoma cells

Authors

  • Gregory B. Lesinski
    • Division of Hematology and Oncology, Department of Internal Medicine, Arthur G. James Cancer Hospital, Richard J. Solove Research InstituteThe Ohio State University
  • Kristen Benninger
    • Division of Surgery, Arthur G. James Cancer Hospital, Richard J. Solove Research InstituteThe Ohio State University
  • Melanie Kreiner
    • Division of Surgery, Arthur G. James Cancer Hospital, Richard J. Solove Research InstituteThe Ohio State University
  • Megan Quimper
    • Division of Surgery, Arthur G. James Cancer Hospital, Richard J. Solove Research InstituteThe Ohio State University
  • Gregory Young
    • The Center for Biostatistics, Arthur G. James Cancer Hospital, Richard J. Solove Research InstituteThe Ohio State University
    • Division of Surgery, Arthur G. James Cancer Hospital, Richard J. Solove Research InstituteThe Ohio State University
Original Article

DOI: 10.1007/s00262-009-0710-y

Cite this article as:
Lesinski, G.B., Benninger, K., Kreiner, M. et al. Cancer Immunol Immunother (2009) 58: 2031. doi:10.1007/s00262-009-0710-y

Abstract

Bortezomib is a proteasome inhibitor that can synergize with interferon-alpha (IFN-α) to induce apoptosis in melanoma cells in vitro and inhibit tumor growth in vivo. We hypothesized that proteasome inhibition may be an effective means to sensitize melanoma cells to the direct effects of IFN-α. Pre-treatment of human melanoma cells with bortezomib led to significantly increased transcription of interferon-stimulated genes as determined by real-time PCR. Flow cytometric and immunoblot analyses indicated that the enhanced direct actions of IFN-α on melanoma cells were the result of prolonged phosphorylation of STAT1 (P-STAT1) on both the Tyrosine701 and Serine727 residues. In contrast, the enhanced IFN-α-induced P-STAT1 was not observed in peripheral blood mononuclear cells that were pre-treated with bortezomib. These data suggest that proteasome inhibition represents a mechanism to enhance the direct effects of IFN-α on melanoma cells thereby complementing its immunostimulatory properties.

Keywords

BortezomibProteasome inhibitionInterferonSTAT1Melanoma

Copyright information

© Springer-Verlag 2009