Extended Data Fig. 10: Inhibition of PKR and GCN2 reduces viability and p-eIF2α levels in patient-derived CRC organoids.
(a) Growth of patient-derived CRC organoids treated with GCN2 and PKR inhibitors, representative of three independent experiments with similar results. Seven different patient-derived organoid lines were grown for two or three days, and then treated with A-92 or C16 for 96 h at the indicated concentrations. DMSO was used as solvent control. Scale bars = 200 µM. (b) Immunoblot of three patient-derived CRC organoid lines (upper). Organoids were treated with C16 (1 µM) or A-92 (3 µM) for 6 h. DMSO (D) was used as solvent control. Quantification of p-eIF2α S51 levels, normalised to eIF2α (lower). Data show mean ± s.d. (n = 3 biologically independent organoid lines); unpaired, two-tailed t-test. (c) Annexin V/PI FACS of shCTR-transduced, PKR- or GCN2-depleted APCdef cells (96 h ethanol) after treatment with DMSO, A-92 or C16 for 48 h. Data shown mean ± s.d. (n = 3 biologically independent experiments); unpaired, two-tailed t-test. Unprocessed immunoblots are shown in Source Data Extended Data Fig. 10.
