PK-11195 (PK) and bortezomib treatment triggers synergistic anti-MM activity in MM cell lines and patient MM cells. (A) Dex-sensitive (MM.1S, ▪) and Dex-resistant (MM.1R, □) cells were treated with various concentrations of bortezomib (1-10 nM) for 24 hours and assessed for viability using MTT assays. Results are means ± SDs of 3 independent experiments (P < .005). (B) MM.1S (▪) and MM.1R (□) cells were treated with various concentrations of PK (25-200 μM) for 24 hours and assessed for viability using MTT assays. Results are means ± SDs of 3 independent experiments (P < .005). (C) MM.1S and MM.1R cells were treated with PK (50 μM), bortezomib (2 nM), or PK + bortezomib for 24 hours and assessed for viability using MTT assays (P = .05 for MM.1S cells and P = .04 for MM.1R cells, one-sided Wilcoxon rank-rank sum test). Error bars indicate standard error. (D) MM.1S cells were treated with PK (50 μM), bortezomib (2 nM), or PK + bortezomib for 24 hours and assessed for apoptosis by Annexin V staining assays. Results are means ± SDs of 3 independent experiments (P < .003). (E) MM.1S cells were treated with PK (50 μM), bortezomib (2 nM), or PK + bortezomib for 24 hours and assessed for apoptosis by PARP cleavage assays. Total protein lysates were subjected to SDS-PAGE analysis. Immunoblot analysis of the lysates was performed with anti-PARP Abs. FL indicates full length; CF, cleaved fragment. (F) MM.1S cells were treated with PK (50 μM), MG-132 (50 μM), or PK + MG-132 for 24 hours and assessed for viability using MTT assays. Results are means ± SDs of 3 independent experiments (P < .005).