DUSP4 promotes doxorubicin resistance in gastric cancer through epithelial-mesenchymal transition
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Xing Kang1,*, Minhuan Li2,*, Hao Zhu3,*, Xiaofeng Lu1, Ji Miao1, Shangce Du1, Xuefeng Xia1 and Wenxian Guan1
1Department of General Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
2Department of Laboratory Medicine, Sir Run Run Hospital, Nanjing Medical University, Nanjing, 210000, Jiangsu Province, China
3Department of Gastroenterology, The Afflicted Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
*These authors have contributed equally to this work
Xuefeng Xia, email: firstname.lastname@example.org
Wenxian Guan, email: email@example.com
Keywords: chemoresistance, doxorubicin, DUSP4, epithelial-mesenchymal transition, gastric cancer
Received: August 08, 2017 Accepted: September 03, 2017 Published: October 04, 2017
Chemoresistance limits treatment efficacy in gastric cancer and doxorubicin resistance is common in gastric cancer cells. Dual specificity phosphatase 4 (DUSP4) has been associated with tumor progression. This study aimed to investigate the mechanism of DUSP4 regulating doxorubicin resistance in gastric cancer cells. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay were used to measure cell viability and proliferation in gastric cancer cells treated with doxorubicin. The expression of DUSP4, E-cadherin and Vimentin protein was detected by Western blotting. Overexpression of DUSP4 was more resistant to doxorubicin in gastric cancer cells. Knockdown of DUSP4 increased the sensitivity of gastric cancer cells to doxorubicin. Moreover, up-regulation of DUSP4 promoted the Epithelial-Mesenchymal Transition (EMT) in gastric cancer cells, but blocking the EMT using a Twist siRNA increased the sensitivity of gastric cancer cells to doxorubicin and confirmed the EMT was involved in DUSP4-mediated doxorubicin resistance. These findings demonstrated that DUSP4 could enhance doxorubicin resistance by promoting EMT in gastric cancer cells.
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