Open AccessDeguelin inhibits epithelial‐to‐mesenchymal transition and metastasis of human non‐small cell lung cancer cells by regulating NIMA‐related kinase 2
Author(s) -
Zhao Dejian,
Han Wenzheng,
Liu Xia,
Cui Dawei,
Chen Yu
Publication year - 2017
Publication title -
thoracic cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 28
eISSN - 1759-7714
pISSN - 1759-7706
DOI - 10.1111/1759-7714.12444
Subject(s) - cancer research , epithelial–mesenchymal transition , vimentin , metastasis , gene knockdown , cell , cell growth , cell migration , cell culture , kinase , biology , chemistry , medicine , cancer , microbiology and biotechnology , immunology , immunohistochemistry , biochemistry , genetics
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.