Abstract
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.
Highlights
Gastric cancer (GC) is one of the most common digestive system malignancies and has a high mortality rate, accounting for approximately 9% of cancer deaths worldwide [1]
Up-regulation of Dual specificity phosphatase 4 (DUSP4) promoted the EpithelialMesenchymal 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
DUSP4high KATO III and MKN45 cells were more resistant to DOX than DUSP4low BGC and SGC7901 cells
Summary
Gastric cancer (GC) is one of the most common digestive system malignancies and has a high mortality rate, accounting for approximately 9% of cancer deaths worldwide [1]. Most patients with newly diagnosed GC have advanced stage disease that is not resectable [2, 3]. Patients who undergo complete tumor resection have a high risk of recurrence [4]. Chemotherapy has been widely adopted to prolong survival in patients with advanced GC. The overall survival rate of advanced GC remains unsatisfactory due to the development of multidrug resistance [5, 6]. The mechanisms underlying chemotherapy resistance in GC are of major interest
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
