Cancer Immunology, Immunotherapy

, Volume 58, Issue 12, pp 2031–2037

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

  • Gregory B. Lesinski
  • Kristen Benninger
  • Melanie Kreiner
  • Megan Quimper
  • Gregory Young
  • William E. CarsonIII
Original Article

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

Bortezomib Proteasome inhibition Interferon STAT1 Melanoma 

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Gregory B. Lesinski
    • 1
  • Kristen Benninger
    • 2
  • Melanie Kreiner
    • 2
  • Megan Quimper
    • 2
  • Gregory Young
    • 3
  • William E. CarsonIII
    • 2
  1. 1.Division of Hematology and Oncology, Department of Internal Medicine, Arthur G. James Cancer Hospital, Richard J. Solove Research InstituteThe Ohio State UniversityColumbusUSA
  2. 2.Division of Surgery, Arthur G. James Cancer Hospital, Richard J. Solove Research InstituteThe Ohio State UniversityColumbusUSA
  3. 3.The Center for Biostatistics, Arthur G. James Cancer Hospital, Richard J. Solove Research InstituteThe Ohio State UniversityColumbusUSA

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