MK0752 在 HPV 阳性头颈部鳞状细胞癌中的体外抗肿瘤作用。
In vitro antineoplastic effects of MK0752 in HPV-positive head and neck squamous cell carcinoma.
机构信息
Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Vienna, Vienna, Austria.
Department of Pathology, Medical University of Vienna, Vienna, Austria.
出版信息
J Cancer Res Clin Oncol. 2023 Nov;149(16):14691-14699. doi: 10.1007/s00432-023-05269-x. Epub 2023 Aug 16.
PURPOSE
Gamma-secretase inhibitor MK0752 has shown a high therapeutic potential in different solid malignant tumors. Up to now, its antineoplastic effects were not investigated in head and neck squamous cell carcinoma (HNSCC) and particularly in human-papillomavirus (HPV)-positive tumors.
METHODS
We conducted cytotoxic, migration, and clonogenic assays in two HPV-negative HNSCC cell lines (Cal27 and FaDu) and one HPV-positive cell line (SCC154). Furthermore, in order to assess the pro-apoptotic effects of MK0752, a Caspase 3/7 Glo assay was performed.
RESULTS
Our experiments revealed antineoplastic effects of MK0752 in all three cell lines. Strong cytotoxic and antimigratory potential was shown in all cell lines, with strongest effects observed in the HPV-positive cell line. Meanwhile, anticlonogenic effects were only shown in Cal27 and SCC154. Most importantly, MK0752 induced apoptosis solely in HPV-positive SCC154.
CONCLUSIONS
Our novel findings indicate a therapeutic potential of MK0752 in HPV-positive HNSCC. Indeed, further investigation is needed for validation of our results and for the assessment of the mechanistic background.
目的
γ-分泌酶抑制剂 MK0752 在不同的实体恶性肿瘤中显示出了很高的治疗潜力。迄今为止，其抗肿瘤作用尚未在头颈部鳞状细胞癌（HNSCC）中进行研究，特别是在人乳头瘤病毒（HPV）阳性肿瘤中。
方法
我们在两种 HPV 阴性的 HNSCC 细胞系（Cal27 和 FaDu）和一种 HPV 阳性细胞系（SCC154）中进行了细胞毒性、迁移和集落形成试验。此外，为了评估 MK0752 的促凋亡作用，我们进行了 Caspase 3/7 Glo 测定。
结果
我们的实验揭示了 MK0752 在所有三种细胞系中的抗肿瘤作用。在所有细胞系中均显示出强烈的细胞毒性和抗迁移潜力，在 HPV 阳性细胞系中观察到最强的效果。同时，仅在 Cal27 和 SCC154 中观察到抗集落形成作用。最重要的是，MK0752 仅在 HPV 阳性的 SCC154 中诱导凋亡。
结论
我们的新发现表明 MK0752 在 HPV 阳性的 HNSCC 中有治疗潜力。确实，需要进一步的研究来验证我们的结果，并评估其机制背景。
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