PU-H71 synergizes with a pan-BCL2 family inhibitor. (A) The indicated PEL cell lines were treated with pan-BCL2-family inhibitor obatoclax for 72 hours, and the dose response curves are shown. The fraction of cells killed relative to the untreated control is represented on the y-axis; the obatoclax (Obx) dose is shown in the x-axis. Plots were calculated using Compusyn Software and represent best-fit models of the data point. The R value for the dose-effect curves ranged between 0.94 and 0.97 in all the cell lines. (B) These PEL cells were treated with PUH71, Obx, and a combination of both for 72 hours. Doses were chosen based to the sensitivity of each cell line, and were as follows: BC3, PUH71 0.078125 μM; Obx, 0.15625 μM; BC2, PUH71 and Obx 0.3125 μM; and BC5 and BCBL1, PUH71 and Obx 0.625 μM. (C) BC3 cells treated with PU-H71 or Obx for 48 hours were analyzed for synergy. The isobologram indicates GI₅₀, GI₇₅, and GI₉₀ values (for PUH71, GI50, GI75, and GI90 are 0.29256, 0.83922, and 2.38530 μM, respectively; for Obx, 0.14949, 0.24479, and 0.40084 μM), indicating strong synergy with combination index values of ∼0.2. (D) The fraction affected–combinatorial index plot for the combination of Obx and PU-H71 at 72 hours. The fraction of cells killed is represented on the x-axis (Fa) and the combinatorial index is represented on the y-axis (CI). The dotted line represents an additive effect and divides the antagonistic zone (above) and synergistic zone (below). The points represent actual combination data points and the blue line represents the computer simulation for the relationship.