Fig. 3: RBM15 suppression augments osimertinib sensitivity in resistant LUAD models.

A H1975 cells were exposed to increasing concentrations of osimertinib and cultured for 24 weeks to select H1975-OR cells (top panel). H1975 and H1975-OR cells were incubated with osimertinib for 48 h, cell viability was measured using the CCK-8 assay, and the IC₅₀ was calculated (bottom panel). T test. B Western blot investigation of EGFR, ERK, and AKT protein levels and their phosphorylation. C, D RBM15 protein and mRNA expression levels in H1975 and H1975-OR were assessed using western blot and qRT-PCR. T test. E Osimertinib IC₅₀ of H1975-OR cells transfected with si-NC, si-RBM15#1, or si-RBM15#2. T test. F A schematic diagram for the construction of drug-resistant organoids. G PDO1-OR and osimertinib-sensitive organoids were incubated with osimertinib for 48 h, cell viability was measured using the CCK-8 assay, and the IC₅₀ was calculated. T test. H Osimertinib IC₅₀ value of PDO1-OR transfected with sh-NC or sh-RBM15. T test. I, J Effects of RBM15 knockdown on H1975-OR and PDO1-OR apoptosis assessed using flow cytometry and TUNEL staining. T test. K Western blot analysis of EGFR and AKT proteins and their phosphorylation levels after knockdown of RBM15 and 48-h osimertinib treatment. L Representative images of xenograft tumors from sh-NC, sh-NC + Osi, and sh-RBM15 + Osi groups. M, N Tumor growth curve and tumor weights. T test. O Representative images of Ki-67 positive staining in xenografted tumors. T test. Error bars represent the means ± SDs. *P < 0.05, **P < 0.01, ****P < 0.0001.