Objective       To clarify the role and mechanism of epithelial-mesenchymal transition (EMT) in the sensitivity of non-small cell lung cancer (NSCLC) patients treated with g

efitinib.       Methods      Epidermal growth factor receptor (EGFR) mutations were detected by mutant-enriched PCR assay

and the expression of E-cadherin and fibronectin were evaluated by immunohistochemistry (IHC). Cultured PC9 cells were treated with TGF-β1 for 4 weeks

and the morphological changes were observed by phase-contrast microscopy. MTT assay was used to detect the sensitivity of cells to gefitinib. In addition

the expression of EMT-related marker proteins (E-cadherin and fibronectin) and EGFR downstream signaling molecules (p-ERK

p-AKT and p-STAT3) were assessed by Western blotting.       Results       EGFR gene mutations were identified in 25 of 43 samples (46.51%). The frequency of E-cadherin-positive samples was significantly higher in the samples with EGFR mutants than in those with wild-type EGFR (70.00% vs 30.00%

P

0.05)

and the overall response rate to gefitinib was 46.51% (20/43). The treatment responsiveness in the E-cadherin-positive patients was significantly higher than that in the fibronectin-positive patients (65.00% vs 30.43%

P

0.05). TGF-β1 could induce an EMT morphological alteration and up-regulate the expression of fibronectin in PC9 cells. The sensitivity to gefitinib was decreased in the PC9 cells treated with TGF-β1

and the activation of AKT and STAT3 were observed in vitro.       Conclusion       EMT plays an important role in the resistance to EGFR-tyrosine kinase inhibitors (TKIs). Induction of EMT by TGF-β1 may contribute to the decreased efficacy of gefitinib therapy through sustaining activation of AKT and STAT3.