背景:头颈部鳞状细胞癌(HNSC)是一种危险的癌症,对人类健康构成重要威胁。氯硝柳胺是一种抗蠕虫药物,已获得FDA批准。在药物再利用屏幕中,发现氯硝柳胺抑制一系列肿瘤类型的增殖活性。其在HNSC中的功能作用,然而,尚未建立。方法:采用MTT法和集落形成法,探讨氯硝柳胺对HNSC细胞增殖的影响,而伤口愈合和Transwell试验用于评估迁移和侵入性。流式细胞术和Western免疫印迹分别用于评估细胞凋亡和蛋白质表达模式。HNSC异种移植肿瘤模型系统用于评估氯硝柳胺的体内抗肿瘤活性,和免疫荧光染色用于评估切割的Caspase3和Ki67表达。用肺转移模型评估了氯硝柳胺在体内预防转移进展的能力。结果:这些分析揭示了氯硝柳胺抑制HNSC细胞迁移的能力,扩散,和体外侵袭性,同时促进凋亡死亡。从机械的角度来看,该药物抑制Stat3磷酸化和β-catenin表达,同时增加HNSC细胞中裂解的Caspase3水平并降低Bcl-2水平。重要的是,这种药物能够抑制体内肿瘤生长和肺转移形成,免疫荧光染色证实其降低Ki67水平并增加切割的Caspase3含量。结论:总之,这些分析强调了氯硝柳胺抑制HNSC细胞迁移和增殖活性的能力,同时通过p-Stat3和β-catenin途径失活引起凋亡性死亡.因此,氯硝柳胺有望重新用作HNSC更有效临床管理的候选药物。
Background: Head and neck squamous cell carcinoma (HNSC) is a dangerous cancer that represents an important threat to human health.
Niclosamide is an anti-helminthic drug that has received FDA approval. In drug repurposing screens,
niclosamide was found to inhibit proliferative activity for a range of tumor types. Its functional effects in HNSC, however, have yet to be established. Methods: MTT and colony formation assays were used to explore the impact of
niclosamide on the proliferation of HNSC cells, while wound healing and Transwell assays were employed to assess migration and invasivity. Flow cytometry and Western immunoblotting were respectively used to assess cellular apoptosis and protein expression patterns. An HNSC xenograft tumor model system was used to evaluate the in vivo antitumor activity of
niclosamide, and immunofluorescent staining was employed to assess cleaved Caspase3 and Ki67 expression. The ability of niclosamide to prevent metastatic progression in vivo was assessed with a model of pulmonary metastasis. Results: These analyses revealed the ability of
niclosamide to suppress HNSC cell migration, proliferation, and invasivity in vitro while promoting apoptotic death. From a mechanistic perspective, this drug suppressed Stat3 phosphorylation and β-catenin expression, while increasing cleaved Caspase3 levels in HNSC cells and reducing Bcl-2 levels. Importantly, this drug was able to suppress in vivo tumor growth and pulmonary metastasis formation, with immunofluorescent staining confirming that it reduced Ki67 levels and increased cleaved Caspase3 content. Conclusion: In conclusion, these analyses highlight the ability of niclosamide to inhibit HNSC cell migration and proliferative activity while provoking apoptotic death mediated via p-Stat3 and β-catenin pathway inactivation. Niclosamide thus holds promise for repurposing as a candidate drug for the more effective clinical management of HNSC.