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.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
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 Wdoi
10.3892/ijo.2018.4462subject
Has Abstractpub_date
2018-09-01 00:00:00pages
1138-1148issue
3eissn
1019-6439issn
1791-2423journal_volume
53pub_type
杂志文章abstract::Breast cancer is the leading cause of cancer death among women. Paclitaxel, a mitotic inhibitor, is highly effective in the treatment of breast cancer. However, development of resistance to paclitaxel limits its clinical use. Identifying new compounds and new strategies that are effective against breast cancer, in par...
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