Journal
CANCER LETTERS
Volume 326, Issue 2, Pages 135-142Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2012.07.030
Keywords
Panobinostat; Bortezomib; Leukemia; AKT; NF-kappa B
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In this study, we investigated the synergistic effects of panobinostat and bortezomib on adriamycin-resistant HL60/ADR cells and refractory acute myelogenous leukemia (AML) primary cells. Combination of both agents had synergistic cytotoxicity on these cells, and increased the sensitivity of HL60/ADR cells to adriamycin. Panobinostat plus bortezomib was shown to modulate multiple apoptotic and drug metabolic related molecules, including activation of caspases, down-regulation of XIAP. Bcl-2 and MRP1. These effects were likely to be mediated via inhibition of AKT and NF-kappa B pathways. These findings provide evidence for clinic protocols using panobinostat and borezomib to overcome drug resistance in refractory AML patients. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
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