Liang Dong, Yu Chen, Ma Zhao, Yang Xingye, Li Zhenzhen, Dong Xuhui, Qin Xiaojun, Du Lupei, Li Minyong
Key Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Acta Pharm Sin B. 2022 May;12(5):2429-2442. doi: 10.1016/j.apsb.2021.12.005. Epub 2021 Dec 20.
Head and neck squamous cell carcinoma (HNSCC) is one of the most common human cancers; however, its outcome of pharmacotherapy is always very limited. Herein, we performed a batch query in the connectivity map (cMap) based on bioinformatics, queried out 35 compounds with therapeutic potential, and screened out parbendazole as a most promising compound, which had an excellent inhibitory effect on the proliferation of HNSCC cell lines. In addition, tubulin was identified as a primary target of parbendazole, and the direct binding between them was further verified. Parbendazole was further proved as an effective tubulin polymerization inhibitor, which can block the cell cycle, cause apoptosis and prevent cell migration, and it exhibited reasonable therapeutic effect and low toxicity in the and anti-tumor evaluation. Our study repositioned an anthelmintic parbendazole to treat HNSCC, which revealed a therapeutic utility and provided a new treatment option for human cancers.
头颈部鳞状细胞癌（HNSCC）是最常见的人类癌症之一；然而，其药物治疗的效果一直非常有限。在此，我们基于生物信息学在连通性图谱（cMap）中进行了批量查询，找出了35种具有治疗潜力的化合物，并筛选出帕苯达唑作为最有前景的化合物，它对HNSCC细胞系的增殖具有出色的抑制作用。此外，微管蛋白被确定为帕苯达唑的主要靶点，并进一步验证了它们之间的直接结合。帕苯达唑进一步被证明是一种有效的微管蛋白聚合抑制剂，它可以阻断细胞周期、导致细胞凋亡并阻止细胞迁移，并且在体内和体外抗肿瘤评估中显示出合理的治疗效果和低毒性。我们的研究将一种驱虫药帕苯达唑重新定位用于治疗HNSCC，揭示了其治疗效用，并为人类癌症提供了一种新的治疗选择。
