Open Access

DUSP1 induces apatinib resistance by activating the MAPK pathway in gastric cancer

  • Authors:
    • Fei Teng
    • Zhiyuan Xu
    • Jiahui Chen
    • Guowei Zheng
    • Guodian Zheng
    • Hang Lv
    • Yiping Wang
    • Lijing Wang
    • Xiangdong Cheng
  • View Affiliations

  • Published online on: June 25, 2018     https://doi.org/10.3892/or.2018.6520
  • Pages: 1203-1222
  • Copyright: © Teng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dual‑specificity phosphatase‑1 (DUSP1) is an oncogene that is associated with cancer progression following drug resistance. In order to investigate the potential relationship between DUSP1 and apatinib resistance in gastric cancer cells, we preformed many assays to study this problem. DUSP1 gene was detected by RT‑qPCR assay, proteins in MAPK pathway were quantified by western blot assay, and CCK‑8 assay, flow cytometry and Hoechest 33342 stain were performed to detect the resistance of cells, cell cycles and apoptosis, respectively. Immunohistochemical staining was used to discover the expression of DUSP1 protein in patients' tumor or paratumor tissues. It was found that apatinib (Apa)‑resistant gastric cancer (GC) cells showed increased expression of DUSP1, whereas the knockdown of DUSP1 in resistant cells resensitized these cells to Apa. The restored sensitivity to Apa was the result of inactivation of mitogen‑activated protein kinase (MAPK) signaling and the induction of apoptosis. The in vitro use of Apa in combination with a DUSP1 inhibitor, triptolide, exerted significant effects 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.
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September-2018
Volume 40 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Teng F, Xu Z, Chen J, Zheng G, Zheng G, Lv H, Wang Y, Wang L and Cheng X: DUSP1 induces apatinib resistance by activating the MAPK pathway in gastric cancer. Oncol Rep 40: 1203-1222, 2018.
APA
Teng, F., Xu, Z., Chen, J., Zheng, G., Zheng, G., Lv, H. ... Cheng, X. (2018). DUSP1 induces apatinib resistance by activating the MAPK pathway in gastric cancer. Oncology Reports, 40, 1203-1222. https://doi.org/10.3892/or.2018.6520
MLA
Teng, F., Xu, Z., Chen, J., Zheng, G., Zheng, G., Lv, H., Wang, Y., Wang, L., Cheng, X."DUSP1 induces apatinib resistance by activating the MAPK pathway in gastric cancer". Oncology Reports 40.3 (2018): 1203-1222.
Chicago
Teng, F., Xu, Z., Chen, J., Zheng, G., Zheng, G., Lv, H., Wang, Y., Wang, L., Cheng, X."DUSP1 induces apatinib resistance by activating the MAPK pathway in gastric cancer". Oncology Reports 40, no. 3 (2018): 1203-1222. https://doi.org/10.3892/or.2018.6520