A combination of all-trans retinoic acid derivative and COX-2 inhibitor has anticancer effects in human pharyngeal carcinoma cells
Le Zhu,
Lei Xiong,
Jianshang Huang,
Chonggui Jiang,
Wentao Xu,
Jing Zhang,
Chaojie Hu,
Ying Zhong,
Zijian Dong,
Feihu Chen,
Huaqing Zhu,
Wei-Ting Kuo,
Feng Cao,
Li Zuo
Affiliations
Le Zhu
Laboratory of Molecular Biology, and Department of Biochemistry, Anhui Medical University, Hefei, Anhui, China; Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China; Department of Otorhinolaryngology Head and Neck Surgery, the Second People's Hopital of Hefei, Anhui, China
Lei Xiong
Laboratory of Molecular Biology, and Department of Biochemistry, Anhui Medical University, Hefei, Anhui, China; Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China
Jianshang Huang
Laboratory of Molecular Biology, and Department of Biochemistry, Anhui Medical University, Hefei, Anhui, China; Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China
Chonggui Jiang
Laboratory of Molecular Biology, and Department of Biochemistry, Anhui Medical University, Hefei, Anhui, China; Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China
Wentao Xu
Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China
Jing Zhang
Laboratory of Molecular Biology, and Department of Biochemistry, Anhui Medical University, Hefei, Anhui, China
Chaojie Hu
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
Ying Zhong
Department of Orthopedics, Hangzhou Red Cross Hospital, Hangzhou, China
Zijian Dong
Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China
Feihu Chen
College of Pharmacy, Anhui Medical University, Hefei, Anhui, China
Huaqing Zhu
Laboratory of Molecular Biology, and Department of Biochemistry, Anhui Medical University, Hefei, Anhui, China
Wei-Ting Kuo
Graduate Institute of Oral Biology, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan; Corresponding author. Graduate Institute of Oral Biology, National Taiwan University, Taipei, Taiwan.
Feng Cao
Department of Otorhinolaryngology Head and Neck Surgery, the Second People's Hopital of Hefei, Anhui, China; Corresponding author.
Li Zuo
Laboratory of Molecular Biology, and Department of Biochemistry, Anhui Medical University, Hefei, Anhui, China; Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, Anhui, China; Corresponding author. Laboratory of Molecular Biology, and Department of Biochemistry, Anhui Medical University, Hefei, Anhui, China.
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.
