In patients who did not undergo chemotherapy or targeted therapy, the expression of DUSP1 in adjacent tissues was higher when compared with that observed in tumor tissues. on inhibiting the expression of DUSP1, growth inhibition, and apoptosis via the inactivation of MAPK signaling. In patients who did not undergo chemotherapy or targeted therapy, the expression of DUSP1 in adjacent tissues was higher when compared with that observed in tumor tissues. In addition, the expression of DUSP1 was higher in the early stages of GC than in the advanced stages. The expression of DUSP1 in tumor tissues was not associated with the survival rate of the patients. Therefore, increased expression of DUSP1 may be responsible for Apa resistance, and DUSP1 may serve as a biomarker for Apa efficacy. In conclusion, inducing the downregulation of DUSP1 may be a promising strategy to overcome Apa resistance. studies have exhibited that DUSP1 inactivates extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 by a dephosphorylation processes (22C25). In several human epithelial tumors, elevated levels of DUSP1 have been reported, including in prostate, colon and bladder cancer (26C28). However, the expression of DUSP1 in tumors progressively decreased with a higher histological grade, indicating that the function and mechanism of DUSP1 in tumors may vary and is complex. In several studies, it has been reported that tumor cell resistance was closely associated with DUSP1, including lung cancer, ovarian cancer, osteosarcoma, breast cancer, hilar cholangiocarcinoma, acute lymphoid system leukemia, prostate cancer and glioma cancer cells (29C38). Upon the expression of DUSP1, the chemotherapeutic resistance of tumor cells is usually enhanced (31). However, if DUSP1 activity is usually decreased, the chemotherapeutic resistance of tumor cells reduces, resulting in tumor cells with higher sensitivity (29). Triptolide, a bioactive ingredient extracted from antitumor activities (72). In the present study, it was exhibited that DUSP1 was associated with drug resistance. TD-106 Even when the single factor of DUSP1 in the MAPK pathway was an inhibitor, the overall physiological changes in resistant cells were more marked in changes of the MAPK pathway. This may explain why Apa combined with triptolide reversed drug resistance from the perspective of MAPK signaling pathways. Therefore, the results of the present study confirmed that downregulation TD-106 of the expression of DUSP1 with triptolide may be a useful strategy to overcome Apa-acquired resistance. In clinical GC specimens from patients who had not received chemotherapy or targeted drugs, the protein levels of DUSP1 were significantly higher in paracarcinoma tissues than in carcinoma tissues (P<0.0001). In addition, Rabbit polyclonal to AKAP5 an increase in the expression of DUSP1 was associated with cancer progression, drug resistance and poor prognosis. In conclusion, DUSP1 may serve as a predictive biomarker for Apa treatment and its increase may be one possible reason for Apa-acquired resistance. Targeting DUSP1 may overcome the impaired efficacy caused by drug resistance and thereby significantly improve the effectiveness of current antitumor drugs. The present study not only exhibited a novel mechanism for acquired resistance in GC, but also provided an effective combinatorial approach to TD-106 overcome Apa-acquired resistance. Acknowledgements I would like to express my sincere thanks to Professor Juqian Guo for the English TD-106 language revisions of this manuscript. Funding The present study was supported by the National Natural Science Foundation of China (grant no. 81573953), the Program of Zhejiang Provincial TCM Sci-tech Plan (grant no. 2016ZZ012), the Zhejiang Provincial Science and Technology Projects (grant no. 2013C03044-4), the Natural TD-106 Science Foundation of Zhejiang Province (grant nos. LY16H280011 and LY13H160027) and the Zhejiang Provincial Medical and Healthy Science and Technology Projects (grant nos. WKJ-ZJ-1728, 2016KYB220 and 2017PY009). Availability of data and materials The datasets used and/or analyzed during the current study are.