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吡唑N-芳基磺酸盐对口腔鳞状癌细胞系的影响及其作用机制:一类新型选择性环氧化酶-2抑制剂

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

作者信息

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

机构信息

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

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

出版信息

Int J Mol Sci. 2025 Sep 12;26(18):8906. doi: 10.3390/ijms26188906.

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 , , and ) 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 , , and 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.

摘要

口腔鳞状细胞癌(OSCC)是一种侵袭性很强的恶性肿瘤,有效治疗选择有限。本研究旨在探索新型吡唑N-芳基磺酸盐衍生物(化合物 、 和 )作为OSCC中选择性环氧合酶-2(COX-2;前列腺素内过氧化物合酶2,PTGS2)抑制剂的治疗潜力。我们使用CCK-8和Transwell实验评估了这些化合物对CAL-27和SAS细胞系的抗增殖和抗迁移作用,同时通过Hoechst 33342染色和流式细胞术评估细胞凋亡。通过RT-qPCR、蛋白质免疫印迹和酶联免疫吸附测定研究分子机制,重点关注COX-2、基质金属蛋白酶2(MMP2)、基质金属蛋白酶9(MMP9)、B细胞淋巴瘤-2(BCL2)、Bax蛋白(BAX)和JAK/信号转导子与转录激活子3(JAK/STAT3)信号通路。结果表明,化合物 、 和 显著抑制细胞增殖和迁移,诱导细胞凋亡,并下调COX-2及其下游靶点的表达。值得注意的是,这些化合物在非洲绿猴肾细胞(VERO细胞)中表现出较低的细胞毒性,表明其具有良好的生物安全性。总之,我们的研究结果表明,吡唑N-芳基磺酸盐衍生物通过靶向COX-2和JAK/STAT3信号通路有效抑制OSCC细胞的生长和迁移,突出了它们作为OSCC潜在靶向治疗药物的前景。

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