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Interferon alpha (IFN-α) and the proteasome inhibitor bortezomib are both clinically indicated for the treatment of specific hematological cancers. Interferons function by controlling the expression of hundreds of genes in multiple pathways. Bortezomib is a reversible 26S proteasome inhibitor that affects multiple signaling pathways selectively in tumor cells and has demonstrated low toxicity in patients. Combination therapy in oncology is a widely practiced treatment methodology that can lead to improved clinical outcomes. We have determined the individual antiproliferative (AP) activities of bortezomib, Type I IFNs (α, β, ω) and Type II IFN (IFN-γ) in the U266 human multiple myeloma cell line by colorimetric and luminescent cell viability assays. The individual effectiveness of each treatment varied in a concentration and time-dependent manner. The IC50 for bortezomib at day 1 (6.8 nM) dropped to 2.3 nM at day 6. The IC50 for Type I IFNs were ng/ml level at day 2 and decreased to pg/ml level at day 6. Combination of each IFN and bortezomib further decreased the IC50 of treatment AP effects. Cell cycle analysis by propidium iodide (PI) staining flow cytometry revealed increased hypodiploid population in the combination treatment. Functional studies revealed a synergy of growth inhibition due to increased apoptosis (Annexin V/PI staining) and caspase 3/7 activation. Overall, Type I IFNs (α, β, ω) displayed greater synergy indices (CI 0.3-0.5) than IFN-γ (CI 0.6-0.7) in both growth inhibitory and apoptotic assays.
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Quick Search
PBL’s improved site search function is defaulted to an exact match.
Search Term Results |
|
IFN beta |
All interferon beta products and related technical information (e.g. technical notes) |
Human IFN beta |
All human interferon products related technical information (e.g. technical notes) |
IL-2 |
All products contain the term “IL-2”, including IL-23 |
IL 2 |
All products contain the term “IL 2”, including IL-23 |
Erythropoietin |
All EPO products and technical information |
Eryth |
All EPO products and technical information |
The results are displayed in best match products grouped in the following product category filters:
Each filter contains sub-categories for further narrowing of your search results
Other web content such as technical notes that contain the Search Term can be displayed by checking the box next to the corresponding filter on the left side of the Search Results Page.