Fig. 2
Adaptive resistance to trametinib in KRAS-mutant NSCLC cells is attributed to the activation of ERK/AKT signaling and RTK signaling. a A549 (KRASG12S), Calu-1 (KRASG12C), H23 (KRASG12C), and H460 (KRASQ61H) cells were treated with 10 nM trametinib for 0, 2, 5, or 10 days and subjected to immunoblotting with the indicated antibodies. b Bubble plot revealing the KEGG pathways enriched with the DEGs from the RNA-seq data of the A549, Calu1, H23, and H460 cell lines after trametinib treatment for 10 days. The area of each circle reflects the proportion of genes related to specific pathways among the DEGs. The color of the circles represents the range of P values. c RTK gene expression changes in A549, Calu1, H23, and H460 cells following treatment with trametinib for 2 days, 5 days, or 10 days relative to the 0-day control. d‒f Gene expression of c-Kit, FGFR2 and PDGFRB was detected via quantitative reverse transcription polymerase chain reaction (qRT‒PCR) in A549, Calu-1, H460 and H23 cells after treatment with 10 nM trametinib for 0, 2, 5, or 10 days. n = 3. g A549, Calu-1, H460 and H23 cells were treated with trametinib monotherapy (10 nM) or trametinib (10 nM) and anlotinib (1 μM) combination therapy for 10 days and subjected to immunoblotting with the indicated antibodies. Relative densitometric values are indicated below each band. All data comparisons were conducted via two-tailed Student’s t test. The data are presented as the means ± SEMs. *P < 0.05, **P < 0.01, ***P < 0.001
