The
epidermal growth factor receptor‑tyrosine
kinase inhibitor (EGFR‑TKI),
gefitinib, is used widely to treat non‑small cell
lung cancer (NSCLC) with EGFR‑activating mutations. Unfortunately, the acquired drug resistance promoted by epithelial‑mesenchymal transition (EMT) markedly limits the clinical effects and remains a major barrier to a cure. Our previous isobaric tags for relative and absolute quantitation‑based proteomics analysis revealed that the E‑cadherin
protein level was markedly upregulated by
triptolide (TP). The present study aimed to determine whether TP reverses the
gefitinib resistance of human
lung cancer cells by regulating EMT. It was revealed that TP combined with
gefitinib synergistically inhibited the migration and invasion of
lung adenocarcinoma cell line A549; the combination treatment had a significantly better outcome than that of TP and
gefitinib alone. Moreover, TP effectively increased the sensitivity of drug resistant A549 cells to
gefitinib by upregulating E‑cadherin
protein expression and downregulating the MMP9, SNAIL, and
vimentin expression levels. The dysregulated E‑cadherin expression of gefitinib‑sensitive cells induced
gefitinib resistance, which could be overcome by TP. Finally, TP combined with
gefitinib significantly inhibited the growth of xenograft
tumors induced using gefitinib‑resistant A549 cells, which was associated with EMT reversal and E‑cadherin signaling activation in vivo. The present results indicated that the combination of TP and TKIs may be a promising therapeutic strategy to treat patients with NSCLCs harboring EGFR mutations.