论文部分内容阅读
目的:总结国内外关于同源重组因子Rad51在人类肿瘤发生、发展中的作用,以及其在肿瘤治疗中应用的研究现状。方法:应用Medline及CNKI期刊全文数据库检索系统,以“同源重组、Rad51和肿瘤”为关键词,检索1993-01-2009-05的相关文献,共检索到英文文献374篇和中文文献14篇。纳入标准:1)同源重组在DNA修复中的作用;2)Rad51及其相关蛋白在同源重组中的作用和机制;3)Rad51蛋白的表达调控,4)Rad51在人类肿瘤发生、发展中的作用和机制以及以Rad51为靶点的治疗策略。根据纳入标准,精选86篇文献,最后32篇文献纳入分析。结果:Rad51蛋白是参与DNA同源重组性修复的关键因子,Rad51蛋白的高水平表达会导致体内DNA同源重组性修复能力的增强,而同源重组机制的功能失调常会导致基因组不稳定和肿瘤的发生。还有许多研究发现,Rad51蛋白表达升高所导致DNA修复能力的增强会导致肿瘤细胞对放疗、化疗和靶向治疗等多种治疗产生耐受。体外研究表明,下调Rad51蛋白表达水平可有效逆转肿瘤耐药和对放疗产生耐受。结论:Rad51是体内参与同源重组性DNA修复的关键因子,Rad51的功能失调与肿瘤的发生、发展以及治疗耐受密切相关,Rad51将会是未来肿瘤临床治疗中重要的潜在靶点。
OBJECTIVE: To summarize the current status of research on the role of Rad51 in the development and progression of human tumors at home and abroad, and its application in cancer therapy. Methods: Using Medline and CNKI full-text database retrieval system, we searched the relevant articles from 1993-01-2009-05 with “homologous recombination, Rad51 and tumor”, and retrieved 374 English articles and Chinese literature 14 articles. Inclusion criteria: 1) the role of homologous recombination in DNA repair; 2) the role and mechanism of Rad51 and its related proteins in homologous recombination; 3) the regulation of Rad51 protein expression; 4) the role of Rad51 in the development and progression of human tumors The role and mechanism of Rad51 as well as the treatment strategy. According to the inclusion criteria, 86 literatures were selected, and the last 32 articles were included in the analysis. Results: Rad51 protein is a key factor involved in DNA homologous recombination repair. The high level expression of Rad51 protein leads to the enhancement of DNA homologous recombination in vivo. The dysfunction of homologous recombination mechanism often leads to genomic instability and tumor happened. Many other studies have found that the increased ability of DNA repair caused by the increased expression of Rad51 protein results in the tumor cells being resistant to various treatments such as radiotherapy, chemotherapy and targeted therapy. In vitro studies have shown that down-regulation of Rad51 protein expression levels can effectively reverse the tumor resistance and tolerance to radiotherapy. Conclusions: Rad51 is a key factor involved in homologous recombination DNA repair in vivo. Rad51 dysfunction is closely related to tumorigenesis, development and treatment tolerance. Rad51 will be an important potential target for the future clinical treatment of cancer.