Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Ibaraki 300-0394, Japan.
Int J Mol Med. 2010 Jan;25(1):25-9.
A group of histone deacetylase (HDAC) inhibitors has been shown to suppress the growth of a variety of human tumor lines in vitro and in vivo and they are among the most promising candidates for anti-cancer therapeutic agents. We investigated the ability of scriptaid, a novel HDAC inhibitor and trichostatin A (TSA) to enhance cell killing by radiation in radioresistant SQ-20B cells derived from human head and neck squamous carcinoma. SQ-20B cells were treated with scriptaid or TSA in combination with radiation. Cell survival was determined by a colony formation assay and protein levels were examined by Western blotting. DNA double strand breaks were measured by a gamma-H2AX focus assay. Radiosensitization was observed for SQ-20B cells incubated with scriptaid at 5 microM or TSA at 0.1 microM for 24 h. Radiosensitization by scriptaid was accompanied by a prolonged retention of gamma-H2AX foci, suggesting that the enhancement of radiation cell killing by scriptaid involved inhibition of DNA double strand break repair. In addition, treatment with scriptaid suppressed expression of Ku80, but not Ku70. Scriptaid may be a useful radiosensitizer in the treatment of radioresistant human carcinomas.
一组组蛋白去乙酰化酶（HDAC）抑制剂已被证明能够在体外和体内抑制多种人类肿瘤细胞系的生长，它们是最有前途的抗癌治疗药物候选物之一。我们研究了新型 HDAC 抑制剂 scriptaid 和 Trichostatin A（TSA）增强人头颈鳞癌细胞来源的耐辐射 SQ-20B 细胞中放射杀伤的能力。用 scriptaid 或 TSA 联合辐射处理 SQ-20B 细胞。通过集落形成实验测定细胞存活率，并通过 Western blot 检测蛋白水平。通过 γ-H2AX 焦点测定法测量 DNA 双链断裂。用 5 μM scriptaid 或 0.1 μM TSA 孵育 SQ-20B 细胞 24 小时可观察到放射增敏作用。Scriptaid 的放射增敏作用伴随着 γ-H2AX 焦点的持续保留，表明 scriptaid 增强辐射细胞杀伤作用涉及抑制 DNA 双链断裂修复。此外，scriptaid 的处理抑制了 Ku80 的表达，但不抑制 Ku70。Scriptaid 可能是治疗耐辐射人类癌的有用增敏剂。
