Lung cancer incidence and mortality rates are amongst the highest of all malignant
tumors worldwide. ARK5 is a member of the human
AMP-activated protein kinase (AMPK) family which is implicated in
tumor survival and progression. The current study was designed to explore the role of ARK5 in resistance of
non-small cell lung cancer (NSCLC) to
cisplatin. We studied the sensitivity of two NSCLC cell lines, NCI-H1229 and A549, to
cisplatin by using proliferation and cell viability assays. We then examined expression of ARK5, Twist, and the epithelial to mesenchymal transition (EMT)
biomarkers,
E-cadherin and
Vimentin, by Western blot and immunofluorescence. We found that ARK5 downregulation significantly increased the
cisplatin chemosensitivity of NSCLC cells, and that NCI-H1299 cells, which express high levels of ARK5 and possess a mesenchymal phenotype, were more resistant to
cisplatin than A549 cells, which show low expression ARK5. Furthermore,
siRNA-mediated silencing of ARK5 resulted in altered EMT patterns in NSCLC cells. These data support a role for ARK5 in regulating EMT in NSCLC cells. Together, our findings suggest that ARK5 is a potential drug target for combating drug resistance and regulating EMT in NSCLC cells.