BMSC-derived exosomes induce drug resistance of MM cells to bortezomib. (A) 5T33MMvt cells in serum medium were treated with naive or 5T33 BMSC-derived exosomes (40 μg/mL) in the absence or presence of JNJ (20 nM) and Dox (4 μM), and indicated concentration of Btz for 48 hours and cell viability was measured. (B) 5T33MMvv cells in serum medium were cultured with naive or 5T33 BMSC-derived exosomes (40 μg/mL) in the absence or presence of Btz for 24 hours, and cell viability was evaluated. (C) 5T33MMvt cells in serum medium were treated with naive or 5T33 BMSC-derived (40 μg/mL) exosomes in the absence or presence of different concentration of Btz for 48 hours, and the percentage of living cells was determined using fluorescence-activated cell sorter staining. (D) 5T33MMvv cells in serum medium were treated with naive or 5T33 BMSC-derived exosomes (40 μg/mL) in the absence or presence of Btz (1.75nM), and the percentage of living cells was measured using fluorescence-activated cell sorter staining. (E) 5T33MMvt cells in serum medium were treated with naive or 5T33 BMSC-derived exosomes (40 μg/mL) in the absence or presence of Btz (2 nM), and apoptosis-related proteins Bcl-2, Bax, caspase-8, caspase-9, caspase-3, and PARP were detected using western blot. The pixel densities of the proteins were quantified from 3 independent experiments and presented by histograms in the right panel. Mean values ± standard deviations for 3 independent experiments are shown.*P < .05; **P < .01; ***P < .001. Cl, cleaved; Fl, full-length; cas-3, caspase-3; cas-8, caspase-8; cas-9, caspase-9.