Open Access

High COX-2 expression contributes to a poor prognosis through the inhibition of chemotherapy-induced senescence in nasopharyngeal carcinoma

  • Authors:
    • Chen Shi
    • Yongjun Guan
    • Liang Zeng
    • Guizhu Liu
    • Yinghong Zhu
    • He Xu
    • Yichen Lu
    • Jiabin Liu
    • Jiaojiao Guo
    • Xiangling Feng
    • Xinying Zhao
    • Weihong Jiang
    • Guancheng Li
    • Guiyuan Li
    • Yun Dai
    • Fengyan Jin
    • Wei Li
    • Wen Zhou
  • View Affiliations

  • Published online on: June 29, 2018     https://doi.org/10.3892/ijo.2018.4462
  • Pages: 1138-1148
  • Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Resistance to radiotherapy and chemotherapy currently represents one of the major reasons for therapeutic failure in nasopharyngeal carcinoma (NPC). However, the mechanisms underlying resistance to chemotherapy in NPC remain unclear. In this study, cell counting assay, cell cycle assay and senescence associated β-galactosidase activity were performed to evaluate cell growth, proliferation and senescence, respectively. We found that the aberrant expression of cyclooxygenase-2 (COX-2) was associated with a poor outcome and recurrance in patients with NPC. In NPC cells, COX-2 overexpression increased cell proliferation, inhibited cellular senescence and resulted in chemoresistance, while the knockdown of COX-2 reduced cell proliferation, promoted cellular senescence and overcame chemoresistance. Furthermore, fibroblasts from COX-2 knockout mice exhibited cellular senescence, particularly when treated with chemotherapeutic agents. Mechanistically, COX-2 interacted with p53 protein and inhibited cellular senescence, which resulted in chemotherapeutic resistance. On the whole, these findings indicate that COX-2 may play a critical role in chemotherapeutic resistance in NPC via the inhibition of chemotherapy-induced senescence via the inactivation of p53. This study provides experimental evidence for the preclinical value of increasing chemotherapy-induced senescence by targeting COX-2 as an effective antitumor treatment in patients with recurrent NPC.
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September-2018
Volume 53 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Shi C, Guan Y, Zeng L, Liu G, Zhu Y, Xu H, Lu Y, Liu J, Guo J, Feng X, Feng X, et al: High COX-2 expression contributes to a poor prognosis through the inhibition of chemotherapy-induced senescence in nasopharyngeal carcinoma. Int J Oncol 53: 1138-1148, 2018
APA
Shi, C., Guan, Y., Zeng, L., Liu, G., Zhu, Y., Xu, H. ... Zhou, W. (2018). High COX-2 expression contributes to a poor prognosis through the inhibition of chemotherapy-induced senescence in nasopharyngeal carcinoma. International Journal of Oncology, 53, 1138-1148. https://doi.org/10.3892/ijo.2018.4462
MLA
Shi, C., Guan, Y., Zeng, L., Liu, G., Zhu, Y., Xu, H., Lu, Y., Liu, J., Guo, J., Feng, X., Zhao, X., Jiang, W., Li, G., Li, G., Dai, Y., Jin, F., Li, W., Zhou, W."High COX-2 expression contributes to a poor prognosis through the inhibition of chemotherapy-induced senescence in nasopharyngeal carcinoma". International Journal of Oncology 53.3 (2018): 1138-1148.
Chicago
Shi, C., Guan, Y., Zeng, L., Liu, G., Zhu, Y., Xu, H., Lu, Y., Liu, J., Guo, J., Feng, X., Zhao, X., Jiang, W., Li, G., Li, G., Dai, Y., Jin, F., Li, W., Zhou, W."High COX-2 expression contributes to a poor prognosis through the inhibition of chemotherapy-induced senescence in nasopharyngeal carcinoma". International Journal of Oncology 53, no. 3 (2018): 1138-1148. https://doi.org/10.3892/ijo.2018.4462