Synergistic effect of panobinostat and bortezomib on chemoresistant acute myelogenous leukemia cells via AKT and NF-κB pathways

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-κB pathways. These findings provide evidence for clinic protocols using panobinostat and borezomib to overcome drug resistance in refractory AML patients.

► We detected that panobinostat and bortezomib had synergistic effects on chemoresistant AML cells. ► The agents in combination increased the sensitivity of HL60/ADR cells to adriamycin. ► We demonstrated that the combined treatment induced apoptosis and drug metabolism. ► These effects were likely to be mediated via inhibition of AKT and NF-κB pathways.