fig5
Figure 5. ZEB2 expression was regulated via the PI3K-Akt pathway in EGFR-TKI-resistant NSCLC. (A) The PI3K-Akt and MAPK signaling pathways were among the most significantly upregulated downstream pathways after EGFR-TKI resistance development in HCC827 and HCC4006 NSCLC cell lines. Common upregulated DEGs of these two cell lines before and after erlotinib resistance were included in this KEGG analysis; (B) The correlation between ZEB2 and key biomarkers of the PI3K-Akt [Akt1(R = 0.203), Akt2(R = 0.173), Akt3(R = 0.609)], MAPK [MAPK(R = 0.314), MAPK8(R = 0.091), MAPK14(R = 0.345)], and NF-κB signaling pathways [NF-κB(R = 0.482), p65(R = 0.169)] were assessed in the LUAD cohort from the TCGA database; (C) Western blotting was conducted to detect the phosphorylation level of key modulators of the PI3K-Akt, MAPK, and NF-κB signaling pathways before and after EGFR-TKI resistance in PC9 and HCC827 cells; (D-F) After 72 h of intervention with gradient concentrations of specific inhibitors of Akt(MK2206), ERK(U0126), and NF-κB(PDTC), western blotting was performed to determine the expression of ZEB2 in PC9-GR and HCC827-GR cells. Representative protein bands and the average results from 3 independent experiments are shown. ***P < 0.0005,
