AMPK-related kinase 5 (ARK5) enhances gemcitabine resistance in pancreatic carcinoma by inducing epithelial-mesenchymal transition

American Journal of Translational Research

Zhengwei Song¹  Xiaoguang Wang²  Fei Chen³ 

[1] Cancer Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310012, Zhejiang, Peoples Repubic of China;Department of Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang, Peoples Repubic of China;Meizhong Disease Gene Research Institute Company Limited, Meizhong, Shandong, Peoples Repubic of China

关键词: ARK5;    pancreatic carcinoma (PC);    GEM;    chemo-resistance;    epithelial-mesenchymal transition (EMT);   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

AMPK-related kinase 5 (ARK5) is a member of the human AMP-activated protein kinase (AMPK) family, which is associated with increased tumor survival and drug resistance in many cancers. However, the function of ARK5 in pancreatic carcinoma (PC) is unclear. Our study investigated the role of ARK5 in the chemo-resistance of PC and its underlying mechanism. PC cell lines that displayed high expression levels of ARK5 had low sensitivity to gemcitabine (GEM). Suppression of ARK5 increased sensitivity to GEM in PC cell lines. Western blotting and immunofluorescence showed that suppression of ARK5 upregulated expression of E-cadherin and downregulated vimentin expression. Suppression of ARK5 also inhibited the epithelial-mesenchymal transition (EMT) efficiency associated with GEM in PC cell lines and upregulation of ARK5 expression enhanced GEM resistance in PC cell lines by inducing Twist-mediated EMT. In addition, we found that suppression of ARK5 increased GEM sensitivity in PC cell lines under hypoxic conditions. ARK5 increases GEM resistance in PC cell lines via EMT, and suppression of ARK5 increases sensitivity to GEM under both normoxic and hypoxic conditions.

【 授权许可】

CC BY-NC