Fig. 4: The combination of pyruvate dehydrogenase kinase (PDK) inhibitors and osimertinib amplifies apoptosis in A549 epidermal growth factor receptor (EGFR) C797S mutant cells.
A549 EGFR19del747_750+T790M+C797S (19DMS)/EGFRL858R+T790M+C797S (RMS) cells were treated with osimertinib (1 μM) alone or in combination with LY294002 (50 μM), YC-1 (50 μM), DCA (15 mM), or leelamine (3 μM) for 24 h. a, b Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. c-e Apoptotic cells were detected using Annexin V/PI staining and flow cytometry; flow cytometry-based dot plots of the Annexin V/PI assay are shown. f Western blotting was performed to evaluate the levels of poly (ADP-ribose) polymerase (PARP), cleaved PARP, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH; loading control). Data information: The data in a, b, and e are presented as the mean ± standard error of the mean (SEM) values. Statistical analyses in a and b were conducted using a one-way analysis of variance with Dunnett’s post hoc test, with comparison to the osimertinib treatment group (sixth lane). Statistical analysis in e was performed using one-way analysis of variance with Dunnett’s post hoc test, with comparison to the control group (the first lane for 19DMS or RMS cells). ***p < 0.001.
