Fig. 2: Osimertinib-resistant non-small cell lung cancers (NSCLCs) exhibit elevated PDK1 expression, followed by enhanced glycolysis.
a Representative immunohistochemical images showing phosphorylated pyruvate dehydrogenase E1 subunit alpha 1 (p-PDHA1) (S293) and pyruvate dehydrogenase kinase 1 (PDK1) in lung cancer tissues of who are osimertinib-sensitive (OS) and osimertinib-resistant (OR) patients. The area in the red box represents a view at 400× magnification. The scale bar represents 200 μm at 100× magnification and 50 μm at 400× magnification. b, f The expression levels of PDK1, PDK2, PDK3, PDK4, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH; loading control) in A549 epidermal growth factor receptor (EGFR) wild-type and mutant cells were measured via western blotting. c, g p-PDHA1 (S293), p-PDHA1 (S300), p-PDHA1 (S232), and total PDHA1 levels in A549 EGFR wild-type and mutant cells were measured via western blotting. d, h PDH activity was measured in A549 EGFR wild-type and mutant cells. e, i Glucose uptake, lactate production, and oxygen consumption rate (OCR) were measured in A549 EGFR wild-type and mutant cells. Data information: The data in a, d, e, h, and i are presented as the mean ± standard error of the mean (SEM) values. Statistical analysis (a, d, e, h and i) was conducted using Student’s t-test for comparisons among the OS, EGFR19del747_750+T790M (19DM), and EGFRL858R+T790M (RM) groups. Statistical analyses in d, e, h, and i were performed using one-way analysis of variance with Dunnett’s post hoc test, with comparison to the wild-type (WT) group. *p < 0.05, **p < 0.01, ***p < 0.001, #p < 0.05, ##p < 0.01, and ###p < 0.001 indicate statistically significant differences. “ns” indicates nonsignificance.
