A histone deacetylase inhibitor, trichostatin A, enhances radiosensitivity by abrogating G2/M arrest in human carcinoma cells.
A histone deacetylase inhibitor, trichostatin A, enhances radiosensitivity by abrogating G2/M arrest in human carcinoma cells.
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DOI：
10.4143/crt.2005.37.2.122
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发表时间：
2005-04-01
影响因子：
4.6
通讯作者：
Park, Charn Il
中科院分区：
文献类型：
--
作者：
Kim, In Ah;Kim, Jin Ho;Park, Charn Il
目的：组蛋白脱乙酰酶抑制剂(HDI)正成为抗癌治疗中潜在的有用成分。在本研究中，我们试图证实曲古抑素A(TSA)对一组人癌细胞株的放射增敏作用，并阐明其相互作用的机制。材料和方法：将A549、HeLa和Caski细胞在照射前18小时暴露于TSA，然后用克隆形成法检测细胞存活率。Western印迹和流式细胞仪分析分别对组蛋白乙酰化、细胞周期和细胞凋亡进行分析。结果：TSA促进组蛋白H3的乙酰化。TSA的预处理对三种细胞系均具有放射增敏作用。TSA处理的细胞在2Gy时的存活分数(SF2)明显低于模型细胞。3种细胞株的增敏率(SER)均呈浓度依赖性增加。结论：TSA可增强一组人癌细胞的放射敏感性，部分原因是TSA抑制了放射诱导的G2/M期阻滞。
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.