期刊
INTERNATIONAL JOURNAL OF ONCOLOGY
卷 53, 期 3, 页码 1138-1148出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2018.4462
关键词
cyclooxygenase-2; senescence; chemotherapy resistance; nasopharyngeal carcinoma
类别
资金
- National Natural Science Foundation of China (NSFC) [81570205, 81400169, 81672993, 81471165]
- Strategic Priority Research Program of Central South University [ZLXD2017004]
- Hunan Province Natural Science Foundation of China (HNSF) [2015JJ2158]
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 -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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