In vitro and in vivo potentiation of radiosensitivity of malignant gliomas by antisense inhibition of the RAD51 gene
In vitro and in vivo potentiation of radiosensitivity of malignant gliomas by antisense inhibition of the RAD51 gene
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DOI：
10.1006/bbrc.1998.8440
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发表时间：
1998-04-17
影响因子：
3.1
通讯作者：
Morita, T
中科院分区：
文献类型：
--
作者：
Ohnishi, T;Taki, T;Morita, T
哺乳动物的RAD 51基因是酵母RAD 51和E. coliRecA基因，其与DNA双链断裂的修复相关，并且还参与重组修复和对γ-辐射和烷基化试剂引起的DNA损伤的各种SOS反应。在这项研究中，我们研究了在体外和体内是否RAD 51基因的反义寡核苷酸（ODNs）抑制增强小鼠恶性胶质瘤的放射敏感性。100 nM的RAD 51反义ODNs抑制mRNA水平超过95%，并降低蛋白表达约70%。用100 nM的RAD 51反义ODNs处理小鼠203 G神经胶质瘤细胞，与对照细胞和用有义或乱序ODNs处理的细胞相比，显著增强了辐射诱导的细胞杀伤。将胶质瘤细胞植入小鼠枕大池后，用RAD 51反义ODNs治疗，小鼠的存活时间比未治疗组明显延长（p
The mammalian RAD51 gene is a homologue of the yeast RAD51 and E. coli RecA genes, which are related to the repair of DNA double-strand breaks and are also involved in recombination repair and various SOS responses to DNA damage by gamma-irradiation and alkylating reagents. In this study, we investigated both in vitro and in vivo whether inhibition of the RAD51 gene by antisense oligonucleotides (ODNs) enhances the radiosensitivity of mouse malignant gliomas. A volume of 100 nM of RAD51 antisense ODNs inhibited the level of mRNA by more than 95% and reduced the protein expression by about 70%. Treatment of mouse 203G glioma cells with 100 nM of RAD51 antisense ODNs significantly enhanced the radiation-induced cell kill compared to control cells, and cells treated with sense or scrambled ODNs. When the glioma cells were implanted in the cisterna magna of mice followed by treatment with RAD51 antisense ODNs, the survival time of the mice was markedly prolonged compared to that of the untreated group (p