Combination of low doses of NPI-0052 and lenalidomide induces synergistic MM-cell death. (A-F) MM-cell lines were pretreated with or without lenalidomide for 24 hours, and then NPI-0052 was added for an additional 24 hours, followed by assessment for cell viability using MTT assays. The experiments with single agents and the respective combinations were carried out simultaneously. The concentrations of drugs, either alone or in combination, were as follows: for MM.1S, KMS12PE, and INA-6 cells: 2nM NPI-0052, 3μM lenalidomide, or NPI-0052 (2nM) plus lenalidomide (3μM); for RPMI-8226 cells: 2nM NPI-0052, 10μM lenalidomide, or NPI-0052 (2nM) plus lenalidomide (10μM); for U266 cells: 5nM NPI-0052, 10μM lenalidomide, or NPI-0052 (5nM) plus lenalidomide (10μM); and for MM.1R cells: 3nM NPI-0052, 5μM lenalidomide, or NPI-0052 (3nM) plus lenalidomide (5μM). *P < .05 for all cell lines. (G-I) MM.1S, RPMI-8226, or INA-6 cells were pretreated with or without lenalidomide for 24 hours, and then NPI-0052 was added for an additional 24 hours and harvested, and whole cell lysates were subjected to immunoblot analysis with anti-PARP, anticaspase-3, antitubulin, or anti-GAPDH Abs. FL indicates full length; and CF, cleaved fragment. Blots shown are representative of 3 independent experiments.