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重新利用阿苯达唑:作为一种对人乳头瘤病毒阴性头颈部鳞状细胞癌具有优先活性的化疗药物的新潜力。

Repurposing Albendazole: new potential as a chemotherapeutic agent with preferential activity against HPV-negative head and neck squamous cell cancer.

作者信息

Ghasemi Farhad, Black Morgan, Vizeacoumar Frederick, Pinto Nicole, Ruicci Kara M, Le Carson Cao Son Huu, Lowerison Matthew R, Leong Hon Sing, Yoo John, Fung Kevin, MacNeil Danielle, Palma David A, Winquist Eric, Mymryk Joe S, Boutros Paul C, Datti Alessandro, Barrett John W, Nichols Anthony C

机构信息

Department of Otolaryngology, London Health Sciences Centre, London, Ontario, Canada.

Department of Oncology, London Health Sciences Centre, London, Ontario, Canada.

出版信息

Oncotarget. 2017 Apr 20;8(42):71512-71519. doi: 10.18632/oncotarget.17292. eCollection 2017 Sep 22.

Abstract

Albendazole is an anti-helminthic drug that has been shown to exhibit anti-cancer properties, however its activity in head and neck squamous cell cancer (HNSCC) was unknown. Using a series of assays, we assessed the ability of albendazole to inhibit proliferation in 20 HNSCC cell lines across a range of albendazole doses (1 nM-10 μM). Cell lines that responded to treatment were further examined for cell death, inhibition of migration and cell cycle arrest. Thirteen of fourteen human papillomavirus-negative HNSCC cell lines responded to albendazole, with an average IC of 152 nM. In contrast, only 3 of 6 human papillomavirus-positive HNSCC cell lines responded. Albendazole treatment resulted in apoptosis, inhibition of cell migration, cell cycle arrest in the G2/M phase and altered tubulin distribution. Normal control cells were not measurably affected by any dose tested. This study indicates that albendazole acts to inhibit the proliferation of human papillomavirus-negative HNSCC cell lines and thus warrants further study as a potential chemotherapeutic agent for patients suffering from head and neck cancer.

摘要

阿苯达唑是一种抗蠕虫药物,已被证明具有抗癌特性,然而其在头颈部鳞状细胞癌(HNSCC)中的活性尚不清楚。我们通过一系列实验,评估了在一系列阿苯达唑剂量(1 nM - 10 μM)下,阿苯达唑抑制20种HNSCC细胞系增殖的能力。对有反应的细胞系进一步检测细胞死亡、迁移抑制和细胞周期阻滞情况。14种人乳头瘤病毒阴性的HNSCC细胞系中有13种对阿苯达唑有反应,平均半数抑制浓度为152 nM。相比之下,6种人乳头瘤病毒阳性的HNSCC细胞系中只有3种有反应。阿苯达唑治疗导致细胞凋亡、细胞迁移抑制、细胞周期阻滞于G2/M期以及微管蛋白分布改变。正常对照细胞在任何测试剂量下均未受到明显影响。本研究表明,阿苯达唑可抑制人乳头瘤病毒阴性的HNSCC细胞系增殖,因此作为头颈部癌症患者的潜在化疗药物值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec47/5641066/ca4790cd5f8b/oncotarget-08-71512-g001.jpg

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