Combined PK and bortezomib treatment triggers synergistic anti-MM activity in human MM cell lines and patient MM cells resistant to conventional drugs, without affecting the viability of normal PBMNCs. (A) MTT assays were performed after incubation of RPMI-8226, doxorubicin-resistant Dox-40, or melphalan-resistant (LR-5) MM cell lines with indicated doses of PK + bortezomib for 24 hours. Results are means ± SDs from 3 independent experiments (P < .0002 for all cells lines). (B) CD138⁺ MM patient cells (patient nos. 1-5) were treated with PK (50 μM), bortezomib (2 nM), or PK + bortezomib for 24 hours and assessed for apoptosis using DNA fragmentation assays. Values are means ± SDs of triplicate samples (P = .05); experiments were repeated 2 times with similar results. (Ci) bortezomib-resistant SUDHL4 (DHL-4) lymphoma cells were treated with indicated concentrations of PK, bortezomib, or PK + bortezomib for 24 hours, and assessed for viability by MTT assays. Results are means ± SDs of 4 independent experiments (P < .005). (Cii) MM.1S cells were stably transfected with Bcl2 construct; treated with indicated concentrations of PK, bortezomib, or PK + bortezomib for 24 hours; and assessed for viability using MTT assays. Results are means ± SDs of 3 independent experiments (P < .005). (D) Normal lymphocytes from 5 healthy donors were treated with PK (50 μM) + bortezomib (2 nM) for 24 hours, and viability was assessed by an MTT assay. Each donor is indicated by a distinct symbol. Results are the mean ± SD of 3 independent experiments (P = .21 from Jonchkeere-Terpstra [J-T] trend test).