Synergistic Activity of Carfilzomib and Panobinostat in Multiple Myeloma Cells via Modulation of ROS Generation and ERK1/2

Figure 5

Lethality of the carfilzomib/LBH589 combination in MM cells was associated with the ROS generation and ERK1/2 inactivation. (a) RPMI 8226 cells were pretreated with or without NAC for 2 h at 37°C and then incubated with carfilzomib (40 nM) and/or LBH589 (4 nM) for 24 h, after which ROS generation was detected. . . (b) ROS generation in RPMI 8226 cells was monitored 0, 4, 9, 18, and 24 hours after combined treatment with carfilzomib (40 nM) and LBH589 (4 nM). . . (c) RPMI 8226 cells were pretreated with or without NAC for 2 h at 37°C and then incubated with or without carfilzomib (40 nM) and LBH589 (4 nM) for 24 h. Apoptosis rate in Cont., LBH589 + CFZ, NAC, and NAC + LBH589 + CFZ group was 6.5% ± 1.9%, 55.3% ± 9.2%, 12.4% ± 4.2%, and 29.2% ± 4.3, respectively. versus LBH589 + CFZ group. . The data shown are representative of three independent experiments. (d) OPM2 and RPMI 8226 cells were treated with carfilzomib (40 nM) and/or LBH589 (4 nM) for 24 h. Then, Western blot analysis of ERK1/2, p-ERK1/2, p38MAPK, and p-p38MAPK was performed. The levels of β-actin were used as the loading control. Cont., control. CFZ, carfilzomib.

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