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. 2018 Apr 24;9(31):21930–21942. doi: 10.18632/oncotarget.25128

Figure 2. EZH2 inhibitor pre-treatment sensitizes HMCLs to panobinostat in a dose-dependent manner.

Figure 2

HMCLs were treated with a combination of the pan-HDAC inhibitor panobinostat and EZH2 inhibitors GSK-126 or EPZ-6438. Viability was measured via CellTiter-Glo® and normalized to untreated controls. Two treatment schedules (represented by schematics in (A) and (B)) were applied and data is represented in the HMCL UTMC2 where EPZ-6438 was either combined with panobinostat simultaneously (A) or 5 days prior to panobinostat (B). Bar plots represent a measurement of synergy quantified by the decrease in the area under the survival curve (AUSC) between panobinostat single agent treatment and combination treatment (where AUSC of each EZH2i+pan/CTRL+pan dose response curve is normalized separately to isolate the shape of the curve from single agent EZH2i toxicity). (C) A panel of HMCLs (n = 24) were treated with panobinostat for 48hrs after a 4-day pre-treatment with either GSK-126 or EPZ-6438. The resulting synergy is represented as decrease in normalized AUSC across the HMCL panel. (D) Three HMCLs representing three levels of EZH2i sensitivity (none, minimal and strong) were pre-treated with a range of EPZ-6438 concentrations for 7 days followed by treatment with a constant range of panobinostat for 48hrs. Viability was measured via CellTiter-Glo®. All error bars represent SEM between biological replicates.