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组蛋白去乙酰化酶抑制剂雷斯替尼对头颈鳞状细胞癌细胞系的影响。

Effect of the histone deacetylase inhibitor resminostat on head and neck squamous cell carcinoma cell lines.

作者信息

Enzenhofer Elisabeth, Kadletz Lorenz, Stanisz Isabella, Kotowski Ulana, Seemann Rudolf, Schmid Rainer, Thurnher Dietmar, Heiduschka Gregor

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria.

Department of Oral and Maxillofacial Surgery, Medical University of Vienna, Vienna, Austria.

出版信息

Head Neck. 2017 May;39(5):900-907. doi: 10.1002/hed.24699. Epub 2017 Feb 7.

DOI:10.1002/hed.24699
PMID:28170128
Abstract

BACKGROUND

Carcinogenesis is determined by various epigenetic events, such as histone deacetylation. The purpose of this study was to investigate the effect of the new histone deacetylase inhibitor resminostat on head and neck squamous cell carcinoma (HNSCC) cell lines.

METHODS

The cytotoxicity of resminostat and cisplatin on HNSCC cell lines SCC25, CAL27, and FaDu was determined using CCK-8 cell proliferation assay and combination index analysis. Cells were irradiated with 2 to 8 Gray. Apoptosis was measured using flow cytometry and expression of Mcl-1, p-AKT, and survivin was investigated.

RESULTS

Treatment with resminostat showed a decrease of cell proliferation of HNSCC cell lines. In addition, a synergistic effect with cisplatin as well as with radiation treatment could be observed. Induction of cell death and dose-dependent downregulation of survivin was evident in all cell lines.

CONCLUSION

Resminostat is a promising treatment of HNSCC because of its antiproliferative, chemosensitizing, and radiosensitizing effects. © 2017 Wiley Periodicals, Inc. Head Neck 39: 900-907, 2017.

摘要

背景

癌症发生由多种表观遗传事件决定,如组蛋白去乙酰化。本研究旨在探讨新型组蛋白去乙酰化酶抑制剂雷斯替尼对头颈鳞状细胞癌(HNSCC)细胞系的影响。

方法

使用CCK-8细胞增殖试验和联合指数分析,测定雷斯替尼和顺铂对HNSCC细胞系SCC25、CAL27和FaDu的细胞毒性。细胞接受2至8格雷的照射。使用流式细胞术检测细胞凋亡,并研究Mcl-1、p-AKT和生存素的表达。

结果

雷斯替尼治疗显示HNSCC细胞系的细胞增殖减少。此外,可观察到与顺铂以及放疗的协同作用。在所有细胞系中,细胞死亡的诱导和生存素的剂量依赖性下调均很明显。

结论

由于雷斯替尼具有抗增殖、化学增敏和放射增敏作用,它是一种有前景的HNSCC治疗药物。© 2017威利期刊公司。《头颈》39: 900 - 907, 2017。

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