| AimAMP-activated protein kinase family member 5 (ARK5) overexpression has been reported in various human cancers, including hepatocellular carcinoma(HCC), and ARK5 is associated with poor prognosis in HCC. ARK5 promoted the proliferation, invasion, metastasis and recurrence of HCC, but the relationship between ARK5 and chemoresistance is unclear. We investigated the role and mechanism of ARKS in the doxorubicin resistance in HCC in this study.Methods and methodWe tested the doxorubicin sensitivity of the Huh7, Hep3B, SNU449, and SNU387 HCC cell lines with CCK-8 kit. Western blotting was used to determine E-cadherin, vimentin, TWIST, and ARK5 expression; E-cadherin and vimentin expression were examined with immunofluorescence simultaneously. Ethynyl deoxyuridine (EdU) assay was used to investigate cell lines proliferation following incubation with the median inhibitory concentration of doxorubicin. To suppress the expression of ARK5 and TWIST in HCC cell lines, siRNA was used to treat the HCC cell lines.Results:1.ARK5 expression was inversely correlated to doxorubicin sensitivity.2.ARK5 knockdown increased HCC cell doxorubicin sensitivity.3.ARK5 regulated the expression of EMT-associated proteins.4.ARK5 suppression reversed EMT in doxorubicin-treated HCC cell lines.5.ARK5 regulated doxorubicin resistance via TWIST.6.ARK5 suppression reversed hypoxia condition induced EMT of HCC.ConclusionsIn the present study, HCC cell lines overexpressing ARK5 displayed low doxorubicin sensitivity. Suppressing ARK5 increased the doxorubicin sensitivity of the cell lines and reversed doxorubicin resistance induced by doxorubicin and hypoxia condition. ARK5 knockdown upregulated E-cadherin and downregulated vimentin, which was consistent with the knockdown of TWIST. ARK5 confers doxorubicin resistance on HCC by inducing epithelial-mesenchymal transition (EMT). |
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