ENHANCEMENT OF RADIATION RESPONSE IN OSTEOSARCOMA AND RHABOMYOSARCOMA CELL LINES BY HISTONE DEACETYLASE INHIBITION
ENHANCEMENT OF RADIATION RESPONSE IN OSTEOSARCOMA AND RHABOMYOSARCOMA CELL LINES BY HISTONE DEACETYLASE INHIBITION
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DOI：
10.1016/j.ijrobp.2010.03.010
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发表时间：
2010-09-01
影响因子：
7
通讯作者：
Weber, Klaus-J.
中科院分区：
文献类型：
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作者：
Blattmann, Claudia;Oertel, Susanne;Weber, Klaus-J.
目的：组蛋白去乙酰化酶抑制剂（HDACIs）可以通过改变许多分子途径来增强细胞对光子辐射治疗（XRT）的敏感性。我们研究了泛HDACIs，如辛二酰苯胺异羟肟酸（SAHA）对两个骨肉瘤（OS）和两个横纹肌肉瘤（RMS）细胞株的辐射反应的影响。方法和材料：克隆形成生存，细胞周期分析，和凋亡进行了检查，在OS（KHOS-24 OS，SAOS 2）和RIM（A-204，RD）细胞系分别与HDACI和HDACI加XRT。通过免疫印迹分析，蛋白质表达进行了研究，细胞周期分析和凋亡的测量进行了流式cytometry.Results：SAHA诱导抑制细胞增殖和克隆形成的生存在OS和RMS细胞系，并导致所有肿瘤细胞系的放射增敏。其他HDACI（如M344和丙戊酸盐）显示出与在一种OS细胞系中研究的相似作用。此外，SAHA显着增加OS细胞系中的辐射诱导的凋亡，而在RMS细胞系中，辐射诱导的凋亡与SAHA无关。在所有研究的肉瘤细胞系，SAHA衰减辐射诱导的DNA修复蛋白的表达（Rad 51，Ku 80）。结论：我们的研究结果表明，HDACIs增强OS和RMS细胞系的辐射作用。HDACIs暴露后DNA修复的抑制以及凋亡诱导的增加可能是HDACIs的放射增敏机制。(C)2010年爱思唯尔公司
Purpose: Histone deacetylase inhibitors (HDACIs) can enhance the sensitivity of cells to photon radiation treatment (XRT) by altering numerous molecular pathways. We investigated the effect of pan-HDACIs such as suberoylanilide hydroxamic acid (SAHA) on radiation response in two osteosarcoma (OS) and two rhabdomyosarcoma (RMS) cell lines.Methods and Materials: Clonogenic survival, cell cycle analysis, and apoptosis were examined in OS (KHOS-24OS, SAOS2) and RIM (A-204, RD) cell lines treated with HDACI and HDACI plus XRT, respectively. Protein expression was investigated via immunoblot analysis, and cell cycle analysis and measurement of apoptosis were performed using flow cytometry.Results: SAHA induced an inhibition of cell proliferation and clonogenic survival in OS and RMS cell lines and led to a significant radiosensitization of all tumor cell lines. Other HDACI such as M344 and valproate showed similar effects as investigated in one OS cell line. Furthermore, SAHA significantly increased radiation-induced apoptosis in the OS cell lines, whereas in the RMS cell lines radiation-induced apoptosis was insignificant with and without SAHA. In all investigated sarcoma cell lines, SAHA attenuated radiation-induced DNA repair protein expression (Rad51, Ku80).Conclusion: Our results show that HDACIs enhance radiation action in OS and RMS cell lines. Inhibition of DNA repair, as well as increased apoptosis induction after exposure to HDACIs, can be mechanisms of radiosensitization by HDACIs. (C) 2010 Elsevier Inc.