组蛋白去乙酰化酶抑制剂曲古抑菌素 A 通过消除人癌细胞的 G2/M 期阻滞增强放射敏感性。
A histone deacetylase inhibitor, trichostatin A, enhances radiosensitivity by abrogating G2/M arrest in human carcinoma cells.
机构信息
Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea.
出版信息
Cancer Res Treat. 2005 Apr;37(2):122-8. doi: 10.4143/crt.2005.37.2.122. Epub 2005 Apr 30.
PURPOSE
Histone deacetylase inhibitors (HDIs) are emerging as potentially useful components in anticancer therapy. In this study, we tried to confirm the radiosensitizing effect of trichostatin A (TSA) on a panel of human carcinoma cell lines and elucidate its mechanism of interaction.
MATERIALS AND METHODS
A549, HeLa and Caski cells were exposed to TSA for 18 hr prior to irradiation, and the cell survival then measured using a clonogenic assay. Western blot and flow cytometric analyses, for histone acetylation, and cell cycle and apoptosis, respectively, were also performed.
RESULTS
TSA increased the acetylation of histone H3. The pretreatment of TSA consistently radiosensitized all three cell lines. The SF2 (surviving fraction at 2 Gy) of TSA-treated cells was significantly lower than that of mock treated cells. The SER (sensitizer enhancement ratio) increased in all 3 cell lines, in concentration dependent manners. The TSA treated cells showed abrogation of radiation-induced G2/M arrest, in a concentration dependent manner.
CONCLUSION
The pretreatment of TSA enhanced the radiosensitivity of a panel of human carcinoma cells, which was attributed, in part, to the abrogation of radiation-induced G2/M arrest.
目的
组蛋白去乙酰化酶抑制剂（HDIs）作为一种有潜力的抗癌治疗药物正在被深入研究。在本研究中，我们尝试验证曲古抑菌素 A（TSA）对一组人癌细胞系的放射增敏作用，并阐明其相互作用的机制。
材料与方法
A549、HeLa 和 Caski 细胞在照射前用 TSA 孵育 18 小时，然后用集落形成实验测量细胞存活率。还进行了 Western blot 和流式细胞术分析，分别用于检测组蛋白 H3 的乙酰化、细胞周期和凋亡。
结果
TSA 增加了组蛋白 H3 的乙酰化。TSA 的预处理一致地增敏了所有三种细胞系。TSA 处理细胞的 SF2（2 Gy 时的存活分数）明显低于对照处理细胞。SER（增敏比）在所有 3 种细胞系中均呈浓度依赖性增加。TSA 处理的细胞表现出辐射诱导的 G2/M 期阻滞的解除，且呈浓度依赖性。
结论
TSA 的预处理增强了一组人癌细胞的放射敏感性，部分原因是辐射诱导的 G2/M 期阻滞的解除。
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