Non‑small cell lung cancer (NSCLC) cells harboring mutations in the epidermal 
growth factor receptor (EGFR) gene initially respond well to EGFR tyrosine 
kinase inhibitors (TKI), including gefitinib. However the tumor cells will 
invariably develop acquired resistance to the drug. The EGFR T790M mutation is 
generally considered to be the molecular genetic basis of acquired TKI 
resistance. The present study aimed to explore how the T790M mutation induces 
tumor cells to escape inhibition by TKI treatment. An acquired 
gefitinib‑resistant cell line (NCI‑H1975/GR) was generated from the NCI‑H1975 
human NSCLC cell line, which harbors the sensitive L858R and resistant T790M 
mutations of EGFR. The resistant cell line was established by exposing the cells 
intermittently to increasing concentrations of gefitinib. The mechanisms by 
which NSCLC acquires resistance to TKIs based on the T790M mutation, were 
investigated by detecting the protein expression levels of the EGFR/Kirsten rat 
sarcoma viral oncogene homolog (KRAS)/v‑Raf murine sarcoma viral oncogene 
homolog B (BRAF) transduction pathway, and epithelial‑mesenchymal transition 
(EMT) with immunocytochemistry. The resistance of the NCI‑H1975/GR cells to 
gefitinib was 2.009‑fold, as compared with the parent cells; however, the 
protein expression levels of EGFR, KRAS and BRAF were lower in the resistant 
cells. Some mesenchymal morphology was observed in the NCI‑H1975/GR cells, 
alongside a decreasing E‑cadherin expression and increasing vimentin expression. 
These results suggest that the reactivation of the EGFR/KRAS/BRAF transduction 
pathway was not detected in the NCI‑H1975/GR cells. EMT may have an important 
role in the development of acquired resistance to EGFR‑TKIs in NSCLC cells with 
sensitivity and resistance mutations.