Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro
Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro
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DOI：
10.1007/s00432-005-0052-x
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发表时间：
2006-02-01
影响因子：
3.6
通讯作者：
Lee, SH
中科院分区：
文献类型：
--
作者：
Kim, SJ;Kim, MS;Lee, SH
目的：抗疟药青蒿素也通过与亚铁原子反应形成自由基而具有癌症特异性细胞毒作用。在这里，我们研究了双氢青蒿素对胶质瘤细胞的放射增敏作用，并评估了这些作用的一些可能机制。材料与方法：采用不同浓度的双氢青蒿素加辐射处理U373MG胶质瘤细胞，通过克隆生存试验评估放射增敏效果。采用western blot和酶活性分析分别测定抗氧化酶、谷胱甘肽- s -转移酶（GST）的表达和活性。结果：双氢青蒿素对胶质瘤细胞系的细胞毒性高于肝癌、乳腺癌和宫颈癌细胞系。在克隆生存试验中，单用双氢青蒿素剂量依赖性地减少了U373MG菌落的数量，而单用双氢青蒿素加γ辐照的克隆存活率远低于单用辐射或双氢青蒿素处理的培养。双氢青蒿素的放射增敏作用被自由基清除剂NAC和TIRON显著阻断，提示与双氢青蒿素诱导的ROS生成有关。此外，双氢青蒿素可抑制辐射诱导的内源性GST的表达。结论：综上所述，我们的研究结果强烈表明，双氢青蒿素可以触发ROS的产生并抑制GST活性，从而导致人类胶质瘤细胞有效且与治疗相关的放射增敏。
Purpose: The antimalarial agent, artemisinin, also confers cancer-specific cytotoxic effects by reacting with ferrous iron atoms to form free radicals. Here, we investigated the radiosensitizing effects of dihydroartemisinin on glioma cells and assessed some possible mechanisms for these effects. Materials and methods: U373MG glioma cells treated with various concentrations of dihydroartemisinin plus radiation, and efficiency of radiosensitization was assessed by clonogenic survival assay. Expression and activity of antioxidant enzymes, glutathione-S-transferase (GST) were quantified by western blot and enzymatic activity analyses, respectively. Results: Dihydroartemisinin showed higher cytotoxicity in the glioma cell lines than in the liver, breast or cervical cancer cell lines. In clonogenic survival assays, treatment with dihydroartemisinin alone dose-dependently reduced the number of U373MG colonies, while treatment with dihydroartemisinin plus gamma-irradiation showed far lower clonal survival than cultures treated with radiation or dihydroartemisinin alone. The radiosensitizing effect of dihydroartemisinin was blocked significantly by the free radical scavengers, NAC and TIRON, indicating association with dihydroartemisinin-induced ROS generation. In addition, the radiation-induced expression of endogenous GST was suppressed by treatment with dihydroartemisinin. The radiosensitizing effect of dihydroartemisinin was also markedly enhanced by the addition of holotransferrin Conclusion: Taken together, our results strongly suggest that dihydroartemisinin triggers production of ROS and inhibits GST activity, leading to effective and therapeutically relevant radiosensitization of human glioma cells.