Fig. 5: Combined targeting of PDK1 inhibits xenograft tumor formation and increases osimertinib sensitivity in A549 EGFR C797S mutant cells.
a Pyruvate dehydrogenase kinase (PDK)1 sgRNA was transfected into A549 EGFR19del747_750+T790M+C797S (19DMS)/EGFRL858R+T790M+C797S (RMS) cells, and PDK1 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH; loading control) expression was measured by immunoblotting. b Treatment of A549 EGFR19del747_750+T790M+C797S (19DMS), 19DMSPDK1 KO1, and 19DMSPDK1 KO2 cells with osimertinib for 72 h, followed by measurement of cell viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. c Treatment of A549 EGFRL858R+T790M+C797S (RMS), RMSPDK1 KO1, and RMSPDK1 KO2 cells with osimertinib for 72 h, followed by the measurement of cell viability using the MTT assay. d–j A549 19DMS (left) or A549 19DMSPDK1 KO1 (right) cells (1 × 107) suspended in 100 μL of sterile phosphate-buffered saline were injected subcutaneously into BALB/c nude mice. Mouse body weight (d) and tumor volume (e) were monitored. Representative images of mice (f, g) and tumors (h). Tumor volume (i) and tumor weight (j). Data information: The data in b, c, e, i, and j are presented as the mean ± standard error of the mean (SEM) values. Statistical analyses in b, c were conducted using Student’s t-test, with comparison to the control group (b, 19DMS; c, RMS). Statistical analyses in e, i, and j were performed using Student’s t-test, with comparison to the 19DMS group. ***p < 0.001.
