Cyclooxygenase‑2 expression is associated with chemoresistance through cancer stemness property in hypopharyngeal carcinoma

Saito,Shin; Ozawa,Hiroyuki; Imanishi,Yorihisa; Sekimizu,Mariko; Watanabe,Yoshihiro; Ito,Fumihiro; Ikari,Yuichi; Nakahara,Nana; Kameyama,Kaori; Ogawa,Kaoru

doi:10.3892/ol.2021.12794

Cyclooxygenase‑2 expression is associated with chemoresistance through cancer stemness property in hypopharyngeal carcinoma

Authors:
- Shin Saito
- Hiroyuki Ozawa
- Yorihisa Imanishi
- Mariko Sekimizu
- Yoshihiro Watanabe
- Fumihiro Ito
- Yuichi Ikari
- Nana Nakahara
- Kaori Kameyama
- Kaoru Ogawa
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Affiliations: Department of Otorhinolaryngology‑Head and Neck Surgery, Keio University School of Medicine, Tokyo 160‑8582, Japan, Department of Otorhinolaryngology‑Head and Neck Surgery, International University of Health and Welfare, Narita, Chiba 286‑8582, Japan, Department of Otorhinolaryngology‑Head and Neck Surgery, National Hospital Organization Tokyo Medical Center, Tokyo 152‑8902, Japan, Department of Otorhinolaryngology‑Head and Neck Surgery, Kawasaki Municipal Kawasaki Hospital, Kawasaki, Kanagawa 210‑0013, Japan, Department of Otorhinolaryngology‑Head and Neck Surgery, Saitama City Hospital, Saitama 336‑8522, Japan, Department of Pathology, Keio University School of Medicine, Tokyo 160‑8582, Japan
Published online on: May 17, 2021 https://doi.org/10.3892/ol.2021.12794
Article Number: 533
Copyright: © Saito et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cyclooxygenase‑2 (COX‑2) is one of the two isoforms of COX, an enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. COX‑2 is associated with the progression in various types of cancer, and its expression has been associated with a poor prognosis in head and neck squamous cell carcinoma (HNSCC). Furthermore, COX‑2 expression has been associated with resistance to anticancer drugs. However, the precise mechanism of COX‑2 for chemoresistance in HNSCC has not been fully elucidated. The present study aimed to investigate the effect of COX‑2 on cancer stem cell (CSC) property and to reveal its effect on chemoresistance using in vitro and clinicopathological assays in HNSCC cells and tissues. The current study analyzed the immunohistochemical expression levels of COX‑2 and clinicopathological factors using matched samples of pretreatment biopsy and surgical specimens from patients with hypopharyngeal carcinoma who underwent tumor resection with preoperative chemotherapy, including docetaxel. Additionally, the chemoresistance to docetaxel with or without a COX‑2 inhibitor (celecoxib) was examined in HNSCC cell lines by MTS assays. To evaluate the association of COX‑2 expression with stemness property, the expression levels of CSC‑associated genes after exposure to celecoxib were assessed by reverse transcription‑quantitative PCR. A sphere formation assay was also performed using ultra‑low attachment dishes and microscopic imaging. The immunohistochemical analysis of biopsy specimens revealed a negative association between COX‑2 expression in biopsy specimens and the pathological effect of induction chemotherapy in surgical specimens. The cell survival rate under exposure to docetaxel was decreased by the addition of celecoxib. COX‑2 inhibition led to downregulation of CSC‑associated gene expression and sphere formation. The present findings suggested that COX‑2 expression may be associated with chemoresistance through the cancer stemness property, and inhibition of COX‑2 may enhance chemo‑sensitivity in HNSCC. Therefore, COX‑2 may be an attractive target for the treatment of HNSCC.

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