IGF-1R signaling mediates resistance to bortezomib. Expression of IGF-1Rα/β was suppressed in RPMI 8226.wt and 8226.BR cells by infecting them with Lentiviral vectors expressing receptor-specific shRNAs. These cells (1 × 104/well) were then plated in 96-well plates, bortezomib was added at the indicated concentrations for 24 hours, and either the WST-1 assay (A) or Western blotting (B) was performed. Data presented are representative from experiments performed in triplicate. ANBL-6.wt cells overexpressing IGF-1R protein (IGF-1R OE) were treated with bortezomib for 24 hours, and levels of apoptosis (C) and activated caspase-3 (D) were measured using fluorescence-activated cell sorting analysis. IGF-1R–overexpressing cell results were then compared with vector control ANBL-6.wt cells. Data shown are the mean of duplicate experiments ± SD.