1. FL cells are dependent on BCL6 in a NOTCH2-dependent manner.
FL cells are dependent on BCL6 in a NOTCH2-dependent manner. A, DoHH2, Sc-1, and WSU-DLCL2 FL cell lines were exposed to six concentrations of RI-BPI (from 1 to 40 μmol/L) or vehicle (water) for 48 hours. The x-axis shows the dose of RI-BPI. The y-axis shows the fractional effect of RI-BPI versus control on cell viability. The experiment was done in triplicate. The dose (in μmol/L) that inhibited cell growth by 50% (GI50) is shown next to each cell line. B, Luminescent caspase-7 and -3 activity assays were performed in FL cell lines (x-axis) exposed to vehicle (gray columns) or RI-BPI 10 μmol/L (black columns) for 24 hours. Results are expressed in percentage of relative luciferase units (RLU) to control (y-axis). C, DoHH2, Sc-1, SU-DHL-4, and OCI-Ly1 cells were transfected NOTCH2 siRNA, BCL6 siRNA, or both as indicated, and cell viability was measured at 48 and 72 hours. The y-axis represents percentage cell viability, normalized to control siRNA (siC; dotted line). D, DoHH2 cells were transfected with NOTCH2 siRNA as indicated and control siRNA as indicated, 24 hours after transfection cells were treated with 10 μmol/L RI-BPI and 24 hours after treatment cell viability was measured as described before. The figure shows the mean of 3 experiments with SEM. E, DoHH2 and SU-DHL-4 cells were pretreated with anti-IgG1 or NOTCH2 antagonist antibody NRR2 for 24 hours and then exposed to 10 μmol/L RI-BPI or control peptide (CP). The y-axis represents viability (at 24 and 48 hours) relative to control antibody (anti-IgG1) treated with CP. All experiments, unless otherwise indicated, were performed in triplicate; the error bars, SEM. Statistical significance is shown (P value one-tailed t test): *, P < 0.05; **, P < See Supplementary Figs. S6 and S7 for additional data.
Ester Valls et al. Cancer Discov 2017;7:
©2017 by American Association for Cancer Research