Napsin A is negatively associated with EMT‑mediated EGFR‑TKI resistance in lung cancer cells.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‑TKI) have been used as a standard therapy for patients with lung cancer with EGFR‑activating mutations. Epithelial‑mesenchymal transition (EMT) has been reported to be associated with the development of EGFR‑TKI resistance, which limits the clinical efficacy of EGFR‑TKI. Therefore, investigating the resistance‑associated mechanism is required in order to elucidate an effective therapeutic approach to enhance the sensitivity of lung cancer to EGFR‑TKI. In the present study, EGFR‑TKI erlotinib‑sensitive H358, H322 and H441 lung cancer cells, erlotinib‑moderately sensitive A549 cells, and erlotinib‑insensitive HCC827 cells with EGFR‑mutation (exon 19 deletion) were used to detect the mRNA and protein expression of the EMT‑associated proteins E‑cadherin and vimentin, and napsin A, by reverse transcription‑quantitative polymerase chain reaction analysis and western blotting. It was observed that the E‑cadherin expression level in erlotinib‑sensitive cells was increased compared with the moderately sensitive A549 cells and HCC827 cells; however, vimentin exhibited opposite expression, suggesting a correlation between EMT and erlotinib sensitivity in lung cancer cells. The napsin A expression level was observed to be positively associated with erlotinib sensitivity. In addition, napsin A highly‑expressingH322 cells were used and napsin A‑silenced cells were constructed using small interfering RNA (siRNA) technology, and were induced by transforming growth factor (TGF)‑βl. It was observed that TGF‑βl partially induced the alterations in E‑cadherin and vimentin expression and the occurrence of EMT in napsin A highly‑expressing cells, while TGF‑βl significantly induced EMT via downregulation of E‑cadherin and upregulation of vimentin in napsin A‑silenced cells; cell proliferation and apoptosis assays demonstrated that TGF‑βl induced marked resistance to erlotinib in napsin A‑silenced cells compared with napsin A‑expression cells. These data indicated that napsin A expression may inhibit TGF‑βl‑induced EMT and was negatively associated with EMT‑mediated erlotinib resistance, suggesting that napsin A expression may improve the sensitivity of lung cancer cells to EGFR‑TKI through the inhibition of EMT.

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