Abstract
Background: Although the cellular and molecular biological effects of interferon (IFN)-α have been well-investigated, the effects of IFN-γ are less understood. Materials and Methods: Eleven human myeloma cell lines with various myeloma-specific chromosomal translocations and overexpression of oncogenes were cultured with 1,000 U/ml of IFN-γ. In the KMS-20 cells, which showed growth inhibition due to IFN-γ, trail expression, status of the Janus kinase (JAK)/STAT pathway were analyzed. Results: KMS-20 cells showed marked up-regulation of trail, activation of STAT1 and TRAIL hyperproduction induced by IFN-γ. Conclusion: The effects of IFN-γ on growth inhibition of KMS-20 cells were characterized by activation of the JAK/STAT signalling pathway, particularly STAT1 phosphorylation, enhanced secretion of TRAIL, and auto/paracrine usage of secreted TRAIL to induce apoptotic cell death. From these results, IFN-γ may be considered one of the drugs to be used in future multidrug chemotherapeutic regimens for myeloma patients.
Footnotes
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↵* Both authors contributed equally to this project.
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Abbreviations: IL, interleukin; IFN, interferon; R, receptor; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand; STAT, signal transducer and activator of transcription; rh, recombinant human; WST-1, water soluble tetrazolium salt-1; JAK, cytokine-activated Janus kinase; DMSO, dimethyl sulfoxide; TUNEL, Terminaldeoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling; RT-PCR, reverse-transcription-polymerase chain reaction; PVDF, polyvinylidene difluoride; HRP, horseradish peroxidase; siRNA, small interfering RNA.
- Received August 2, 2006.
- Revision received October 16, 2006.
- Accepted October 20, 2006.
- Copyright© 2006 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
