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Background  Non‐small cell lung cancer is a lethal malignancy with a high mortality rate. Deguelin displays an anti‐tumor effect and inhibits metastasis in various cancers. The aberrant expression of  NIMA‐related kinase  2 ( NEK 2) indicates poor prognosis and induces epithelial‐to‐mesenchymal transition ( EMT)  and metastasis processes. However, the underlying mechanism between deguelin and  NEK 2 has remained elusive.    Methods   NSCLC  cell lines were treated with deguelin. Wound‐healing and invasion assays were applied to study the inhibitory effect of deguelin on  NSCLC  cells.  EMT  markers,  E ‐cadherin and  V imentin, were also detected by  W estern blot.  NEK 2 protein and messenger  RNA  expression levels were evaluated when  NSCLC  cells were treated with different concentrations of deguelin. The effect of  NEK 2 on  NSCLC  cell metastasis was evaluated through  NEK 2 knockdown. To investigate whether deguelin induced  EMT  by regulating  NEK 2, we overexpressed  NEK 2 in both  NCI ‐ H 520 and  SK ‐ MES ‐1 cell lines, and then used real time‐ PCR  to study the  E ‐cadherin and  V imentin messenger  RNA  expression in both  NSCLC  cells.    Results  Deguelin inhibited migration and invasion processes in  NSCLC  cell lines and decreased  NEK 2 expression in a concentration‐dependent manner. Furthermore,  NEK 2 knockdown inhibited  NSCLC  cell migration and invasion. Finally, overexpressing  NEK 2 in  NCI‐H5 20 and  SK‐MES ‐1 cells could restore the inhibition of metastasis induced by deguelin.    Conclusions  Deguelin could inhibit  EMT  and metastasis, while overexpression of  NEK 2 promotes these processes. Deguelin could decrease  NEK 2 expression, while  NEK 2 overexpression could restore deguelin‐induced inhibition of metastasis.

Deguelin inhibits epithelial‐to‐mesenchymal transition and metastasis of human non‐small cell lung cancer cells by regulating NIMA‐related kinase 2