Fig. 5

Synergistic effect of HDS with melphalan and bortezomib.  A H929 and (B) ARP-1 cells were co-treated with indicated concentration of HDS (12.5–400 µM) and various concentrations of Melphalan (2.5–80 µM) either alone or in combination for 48 h. Cell viability was assessed using a CCK-8 assay (left panel). CI values were calculated based on the median-effect principle. The right graph showed values from the left tables. CI < 1 indicated synergism of HDS and melphalan, as determined using CalcuSyn software. C, D The expression of relative apoptosis (C) and DNA damage proteins (D) of MM cells were monitored by western blot after treated with HDS (50 µM) in the presence (+) or absence (−) of melphalan (10 µM) alone or together. Representative results of triplicate experiments are shown. E, F H929 (E) and ARP-1 (F) cells were treated with bortezomib for 24 h, and then HDS was added for an additional 24 h. Cell viability was assessed using a CCK-8 assay (left panel). CI values were using CalcuSyn software (Right panel). G Primary CD138⁺ cells were isolated from four bortezomib-refractory patients. MM cells were treated with HDS (40 µM) and bortezomib (40 nM) alone or in combination for 48 h, followed by an assessment of cell apoptosis. Representative results of triplicate experiments were shown (left panel). Apoptotic cells were quantified on the right. Data are expressed as means ± SD of three independent experiments. ***P < 0.001