SAHA disrupts bortezomib-induced aggresome formation and augments BZ-induced apoptosis. (A) Multiple myeloma cells form large aggresomes that are disrupted by SAHA. Cells were treated with 5 nM BZ, 2 μM SAHA, or both agents. Cells were then cytocentrifuged onto glass slides, fixed, and stained as described in “Confocal microscopy.” Images were obtained by confocal microscopy. Magnification = 40 ×. (B) Quantification of aggresome formation. Cells were either untreated or treated with SAHA, BZ, or the combination. Aggresomes were present only in cells treated with BZ or BZ + SAHA. Approximately 200 cells were counted and scored as aggresome positive or negative. Mean (n = 3), SD. * indicates a significant difference from values obtained for bortezomib treatment, P < .05. (C) EBV-immortalized B cells are unaffected by the bortezomib and SAHA combination. Cells were treated with 5 nM BZ, 2 μM SAHA, or both agents for 24 hours, and apoptosis was measured by PI-FACS analysis. Mean (n = 3), SD. * indicates a significant difference from control and ** represents a significant difference from single-agent treatments, P < .05.