2. Academic Validation
  3. A combination of all-trans retinoic acid derivative and COX-2 inhibitor has anticancer effects in human pharyngeal carcinoma cells

A combination of all-trans retinoic acid derivative and COX-2 inhibitor has anticancer effects in human pharyngeal carcinoma cells

  • Heliyon. 2023 Nov 17;9(11):e21664. doi: 10.1016/j.heliyon.2023.e21664.
Le Zhu 1 2 3,  Lei Xiong 1 2,  Jianshang Huang 1 2,  Chonggui Jiang 1 2,  Wentao Xu 2,  Jing Zhang 1,  Chaojie Hu 4,  Ying Zhong 5,  Zijian Dong 2,  Feihu Chen 6,  Huaqing Zhu 1,  Wei-Ting Kuo 7 8,  Feng Cao 3,  Li Zuo 1 2
Affiliations

Affiliations

  • 1 Laboratory of Molecular Biology, and Department of Biochemistry, Anhui Medical University, Hefei, Anhui, China.
  • 2 Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China.
  • 3 Department of Otorhinolaryngology Head and Neck Surgery, the Second People's Hopital of Hefei, Anhui, China.
  • 4 Department of Clinical Laboratory, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
  • 5 Department of Orthopedics, Hangzhou Red Cross Hospital, Hangzhou, China.
  • 6 College of Pharmacy, Anhui Medical University, Hefei, Anhui, China.
  • 7 Graduate Institute of Oral Biology, National Taiwan University, Taipei, Taiwan.
  • 8 Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
PMID: 38074870 DOI: 10.1016/j.heliyon.2023.e21664
Abstract

Backgrounds and aims: Carcinogenesis is characterized by an unlimited growth of cells exacerbated by COX-2 overexpression. COX-2 inhibitors have been proven effective in preventing and treating tumors. In our previous studies, we found that 4-Amino-2-Trifluoromethylphenyl Retinate (ATPR) induces cell Apoptosis and inhibits cell proliferation to exhibit anti-cancer properties. The use of ATRA as well as COX-2 inhibitors in clinical settings can cause adverse reactions. It is unknown what the effects and mechanisms of co-administration of ATPR and COX-2 inhibitors are.

Results: A combination of ATPR and COX-2 inhibitors, Celecoxib, inhibited pharyngeal Cancer cell proliferation in vitro and induced Apoptosis. The cell cycle was arrested at G0/G1 by activating P53 and CDNA1. By activating MAPK/JNK pathways, ATPR and Celecoxib led to intrinsic and extrinsic Apoptosis in pharyngeal Cancer cells. ATPR/Celecoxib combined treatment suppressed tumor growth in the pharyngeal Cancer cell-derived xenograft mouse model by increasing the number of apoptotic cells. The expression of the RARA and PTGS2 genes was significantly increased in tumor tissue compared to non-tumor tissue in the clinical analysis of the head and neck squamous cell carcinoma dataset. An association was found between this and the level of intrinsic apoptotic signals. Furthermore, a survival analysis conducted over a period of five years indicated that higher levels of RARA expression were associated with a better clinical outcome.

Conclusion: ATPR and celecoxib inhibit the proliferation of Cancer cells as well as induce Apoptosis. Co-administration of ATPR and COX-2 inhibitors has the potential to be a novel treatment plan for Cancer.

Keywords

ATPR; Celecoxib; Cox-2; Extrinsic and intrinsic apoptosis; MAPK; Pharyngeal cancer; Proliferation.

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