Figure 5. RI-BPI synergizes with Hsp90 inhibitors.

(A) 7 BCL6-dependent DLBCL cell lines (OCI-Ly7, SU-DHL6, OCI-Ly1, Farage, OCI-Ly3, SU-DHL4, and OCI-Ly10) were exposed to 6 concentrations of PU-H71 (from 0.5 to 5 μM), 17-DMAG (from 0.5 to 5 μM), or vehicle control (water or DMSO, respectively) for 48 hours and analyzed for viability. Dose-effect (percentage of dead cells) curves were plotted. The x axis shows the dose of the Hsp90 inhibitor. The y axis shows the fractional effect of the drug as compared with control on cell viability. The experiment was done in 4 replicates. The goodness of fit for the experimental data to the median-effect equation (linear correlation coefficient) obtained from the logarithmic form of this equation was equal or higher than 0.90 for each curve. (B) The same panel of cells was treated with 6 concentrations of PU-H71 or 17-DMAG and the combination of these drugs with 6 concentrations of RI-BPI at a constant ratio. Conservative GI₅₀ isobolograms for the combination of PU-H71 or 17-DMAG with RI-BPI for each drug were plotted. The dose values for each GI₅₀ for each cell line are shown in Supplemental Table 1. (C) The 7 DLBCL cell lines were exposed in triplicate to RI-BPI (10 μM) (white bars), PU-H71 (1 μM) (light gray bars), RI-BPI plus PU-H71 (black bars), or vehicle control (water, dark gray bars, not visible) for 48 hours and analyzed for caspase 7/3 activity. The y axis represents the caspase 7/3 activity as compared with each cell line control (fold). Data are presented as mean with 95% CI.