Effects on Oral Squamous Carcinoma Cell Lines and Their Mechanisms of Pyrazole N-Aryl Sulfonate: A Novel Class of Selective Cyclooxygenase-2 Inhibitors

Wang, Shiqi; Shi, Mingxuan; Wang, Huihui; Zeng, Xianlin; Zhang, Dingtai; Zhang, Zhiyuan; Xu, Zhaoqing; Li, Yi

doi:10.3390/ijms26188906

Open AccessArticle

Effects on Oral Squamous Carcinoma Cell Lines and Their Mechanisms of Pyrazole N-Aryl Sulfonate: A Novel Class of Selective Cyclooxygenase-2 Inhibitors

by

Shiqi Wang

^1,†,

Mingxuan Shi

^1,2,†

,

Huihui Wang

¹,

Xianlin Zeng

¹,

Dingtai Zhang

¹,

Zhiyuan Zhang

¹,

Zhaoqing Xu

^2,* and

Yi Li

^1,*

¹

Key Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing, School of Stomatology, Lanzhou University, Lanzhou 730030, China

²

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730030, China

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2025, 26(18), 8906; https://doi.org/10.3390/ijms26188906

Submission received: 14 July 2025 / Revised: 6 September 2025 / Accepted: 10 September 2025 / Published: 12 September 2025

(This article belongs to the Special Issue Molecular Studies on Oral Disease and Treatment)

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Abstract

Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy with limited effective treatment options. This study aimed to explore the therapeutic potential of novel pyrazole N-aryl sulfonate derivatives (compounds 4b, 4d, and 5f) as selective cyclooxygenase-2 (COX-2; prostaglandin-endoperoxide synthase 2, PTGS2) inhibitors in OSCC. Using CCK-8 and Transwell assays, we evaluated the anti-proliferative and anti-migratory effects of these compounds on CAL-27 and SAS cell lines, while apoptosis was assessed by Hoechst 33342 staining and flow cytometry. Molecular mechanisms were investigated through RT-qPCR, Western blot, and ELISA, focusing on COX-2, MMP2, MMP9, BCL2, BAX, and the JAK/STAT3 pathway. The results demonstrated that compounds 4b, 4d, and 5f significantly inhibited cell proliferation and migration, induced apoptosis, and downregulated the expression of COX-2 and its downstream targets. Notably, these compounds exhibited lower cytotoxicity in VERO cells, indicating favorable biological safety. In conclusion, our findings suggest that pyrazole N-aryl sulfonate derivatives effectively suppress OSCC cell growth and migration by targeting COX-2 and the JAK/STAT3 pathway, highlighting their promise as potential targeted therapeutics for OSCC.

Keywords: pyrazole N-aryl sulfonate derivatives; COX-2; oral squamous cell carcinoma; non-steroidal anti-inflammatory drugs; anti-tumor therapy

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MDPI and ACS Style

Wang, S.; Shi, M.; Wang, H.; Zeng, X.; Zhang, D.; Zhang, Z.; Xu, Z.; Li, Y. Effects on Oral Squamous Carcinoma Cell Lines and Their Mechanisms of Pyrazole N-Aryl Sulfonate: A Novel Class of Selective Cyclooxygenase-2 Inhibitors. Int. J. Mol. Sci. 2025, 26, 8906. https://doi.org/10.3390/ijms26188906

AMA Style

Wang S, Shi M, Wang H, Zeng X, Zhang D, Zhang Z, Xu Z, Li Y. Effects on Oral Squamous Carcinoma Cell Lines and Their Mechanisms of Pyrazole N-Aryl Sulfonate: A Novel Class of Selective Cyclooxygenase-2 Inhibitors. International Journal of Molecular Sciences. 2025; 26(18):8906. https://doi.org/10.3390/ijms26188906

Chicago/Turabian Style

Wang, Shiqi, Mingxuan Shi, Huihui Wang, Xianlin Zeng, Dingtai Zhang, Zhiyuan Zhang, Zhaoqing Xu, and Yi Li. 2025. "Effects on Oral Squamous Carcinoma Cell Lines and Their Mechanisms of Pyrazole N-Aryl Sulfonate: A Novel Class of Selective Cyclooxygenase-2 Inhibitors" International Journal of Molecular Sciences 26, no. 18: 8906. https://doi.org/10.3390/ijms26188906

APA Style

Wang, S., Shi, M., Wang, H., Zeng, X., Zhang, D., Zhang, Z., Xu, Z., & Li, Y. (2025). Effects on Oral Squamous Carcinoma Cell Lines and Their Mechanisms of Pyrazole N-Aryl Sulfonate: A Novel Class of Selective Cyclooxygenase-2 Inhibitors. International Journal of Molecular Sciences, 26(18), 8906. https://doi.org/10.3390/ijms26188906

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Effects on Oral Squamous Carcinoma Cell Lines and Their Mechanisms of Pyrazole N-Aryl Sulfonate: A Novel Class of Selective Cyclooxygenase-2 Inhibitors

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