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

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 (NEK2) indicates poor prognosis and induces epithelial-to-mesenchymal transition (EMT) and metastasis processes. However, the underlying mechanism between deguelin and NEK2 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 Vimentin, were also detected by Western blot. NEK2 protein and messenger RNA expression levels were evaluated when NSCLC cells were treated with different concentrations of deguelin. The effect of NEK2 on NSCLC cell metastasis was evaluated through NEK2 knockdown. To investigate whether deguelin induced EMT by regulating NEK2, we overexpressed NEK2 in both NCI-H520 and SK-MES-1 cell lines, and then used real time-PCR to study the E-cadherin and Vimentin messenger RNA expression in both NSCLC cells.

RESULTS: Deguelin inhibited migration and invasion processes in NSCLC cell lines and decreased NEK2 expression in a concentration-dependent manner. Furthermore, NEK2 knockdown inhibited NSCLC cell migration and invasion. Finally, overexpressing NEK2 in NCI-H520 and SK-MES-1 cells could restore the inhibition of metastasis induced by deguelin.

CONCLUSIONS: Deguelin could inhibit EMT and metastasis, while overexpression of NEK2 promotes these processes. Deguelin could decrease NEK2 expression, while NEK2 overexpression could restore deguelin-induced inhibition of metastasis.