Novel radiation therapy for malignant gliomas based on inhibition of DNA repair

恶性胶质瘤治疗困难的主要原因之一是肿瘤对放射治疗的抵抗。电离辐射可导致DNA双链断裂，导致细胞死亡。但通常情况下，DNA损伤可以通过特定的分子机制修复，包括Ku70分子。因此，抑制Ku70的表达可能恢复放射对肿瘤细胞的抗肿瘤作用。我们通过在恶性胶质瘤细胞中将siRNA转移到HVJ-E载体中来抑制Ku70的表达。与对照组相比，Ku70-siRNA导入的细胞对辐射的敏感性显著增强。此外，将Ku70-siRNA引入荷胶质瘤的裸鼠后进行放射治疗，显著缩小了肿瘤体积，导致小鼠的存活时间比对照组长得多。这些结果表明，抑制DNA双链断裂的修复可能为恶性胶质瘤的放射治疗提供有用的工具。

One of the major reason for difficulty of the treatment of malignant gliomas is resistant to radiotherapy of the tumor. Ionizing radiation can induce double strands breaks in DNA, resulting in cell death. But usually the DNA injury can be repaired by specific molecular mechanisms, including Ku70 molecule. Consequently, inhibition of Ku70 expression may retrieve the anti-tumor effect of radiation on tumor cells. We suppressed the expression of Ku70 by transfer of siRNA in HVJ-E vector in malignant glioma cells. The Ku70-siRNA-introduced cells showed much more enhanced sensitivity for radiation than the control. In addition, radiation therapy after introduction of Ku70-siRNA to glioma-bearing nude mice significantly reduced the tumor volume, resulting in much longer survival of the mice compared to the control. These results suggest that inhibition of the repair of DNA double strand breaks may produce an useful tool for radiation therapy of malignant gliomas.