Fig. 1
From: Induction of synthetic lethality in IDH1-mutated gliomas through inhibition of Bcl-xL
IDH1-R132H-mutated cells are more susceptible to treatment with ABT263. a U87MG glioblastoma cells were transduced with pLPCX IDH1-WT or IDH1-R132H prior to treatment with increasing concentrations of ABT263 for 72 h. Cellular viability was determined by MTT assay and the IC50-values were calculated based on a non-linear regression analysis. Data are presented as mean and SD, n = 3. b T98G glioblastoma cells were transduced with pLPCX IDH1-WT or IDH1-R132H prior to treatment with increasing concentrations of ABT263 for 72 h. Cellular viability was determined by MTT assay and IC50-values were calculated. Data are presented as mean and SD, n = 3. c HCT116 IDH1-WT/IDH1-R132H cells were treated with increasing concentrations of ABT263 for 72 h. Cellular viability and IC50-values were determined based on MTT assay. Data are presented as mean and SD, n = 3. d, e NCH612 (IDH1-R132H) (d) and BT-142 (IDH1-R132H) (e) glioma cells were subjected to treatment with increasing concentrations of ABT263 for 72 h. Cellular viability and IC50-values were determined by CelltiterGlo assay. Data are presented as mean and SD, n = 3. f PPC-2 (IDH1-WT) and PICPG-4 (IDH1-R132H) glioma cells were treated for 48 h with solvent or ABT263 as indicated. Staining with propidium iodide was performed and the fraction of viable cells (100%-SubG1 cells) was determined by flow cytometry. Column: mean. Error bar, SD (n = 3). g–j T98G (g), LN229 (h), SF188 i and MGPP-3 (j) glioblastoma cells were treated for 72 h with solvent, ABT263, 2-HG or the combination of both prior to determining cellular viability by MTT assay. Column: mean. Error bar: SD, n = 3. k–m U87MG cells (k), NCH644 glioma stem-like cells (l) and GBM12 patient-derived xenograft cells (m) were treated for 72 h with indicated combinations of ABT263 and 2-HG. Normalized isobolograms were calculated using the CompuSyn software (ComboSyn, Inc., Paramus, NJ). Data points located on the line indicate an additive drug–drug interaction. Data points located below the line indicate a synergistic drug–drug interaction and data points above the line indicate an antagonistic drug–drug interaction. n Representative microphotographs are provided for SF188 pediatric glioblastoma cells treated for 24 h with solvent, ABT263 and 2-HG as indicated. Scale bar: 100 μm or 20 μm (microphotograph at higher magnification)
