ARK5 promotes doxorubicin resistance in hepatocellular carcinoma via epithelial-mesenchymal transition

AMP-activated protein kinase family member 5 (ARK5) overexpression has been reported in many human cancers, and ARK5 is associated with poor prognosis in hepatocellular carcinoma (HCC). However, whether ARK5 is involved in HCC chemoresistance is unclear. The present study aimed to investigate the role of ARK5 in HCC chemoresistance and the underlying mechanism. In this study, we found that SNU387 and SNU449 HCC cell lines overexpressing ARK5 displayed low doxorubicin sensitivity compared to Huh7 and Hep3B HCC cell lines with ARK5 low-expression. And knockdown of ARK5 increased the doxorubicin sensitivity in all HCC cell lines in the manner of inhibiting cell proliferation. Western blotting and immunofluorescence both showed that ARK5 knockdown upregulated E-cadherin and downregulated vimentin, which was consistent with the knockdown of TWIST, indicating ARK5 was involved in epithelial-mesenchymal transition (EMT). Moreover, suppressing ARK5 by siRNA restored E-cadherin and vimentin expression induced by doxorubicin treatment or hypoxia culture. Our results indicated ARK5 confers doxorubicin resistance in HCC via inducing EMT.