DNA-PK作为放化疗增敏靶点的研究进展

DNA-PK as the target for enhancing sensitivity of radiotherapy and chemotherapy

目的:总结国内外对DNA依赖性蛋白激酶(DNA-dependent protein ki-nase,DNA-PK)作为放化疗增敏靶点研究的现状。方法:检索Medline及CHKD期刊全文数据库检索系统,以"DNA-PK、放射敏感性和化疗敏感性"为关键词,检索1998-01-2008-03关于DNA-PK研究的文献,共检索到英文文献1660篇,中文文献115篇。纳入标准:1)DNA-PK的功能;2)DNA-PK作为肿瘤治疗靶点的研究;3)DNA-PK抑制剂研究。根据纳入标准,精选82篇文献,最后纳入分析35篇文献。结果:放射线和类放射线药物均可导致肿瘤细胞DNA双链断裂(DSB),从而杀伤肿瘤细胞,DNA-PK具有包括促进DSB修复在内的诸多功能。抑制DNA-PK的功能和活性,就可抑制DSB的修复,提高肿瘤细胞对放化疗的敏感性。结论:DNA-PK可以成为肿瘤治疗的理想靶点,但在临床应用方面仍有很多问题需要解决。

OBJECTIVE： To summarize the studies about DNA- dependent protein kinase （DNA-PK） as a target for enhancing radio- and chemo sensitivity of cancer cells. METHODS： Medline and CH KD series full text database retrieval systems were selected with ＂DNA PK, radio-sensitivity, chemo sensitivity＂ as key words, then the articles on DNA-PK study from 1998 01 to 2008-03 were crawled. All 1 660 English articles and 115 Chinses articles were got. Selec tion： the articles about DNA-PK as the target for enhancing radio and chemo sensitivity of cancer cells were chosen; Inclusion criteria： 1） function of DNA-PK. 2） DNA-PK as a target for cancer therapy research. 3） DNA PK inhibitors. Roughing hundreds of articles on DNA-PK and according to the inclusion criteria, 82 articles were se lected, and 35 documents were included in the final analysis. RESULTS： DNA double strand break （DSB） could be induced by irradiation and radiomimetic drugs which could result in cell killing. While DNA-PK have several functions including DSB repair, the inhibition of expression or activity of DNAPK could result in enhancing the chemo- and radio sensitivity. CONCLUSIONS： This review summarizes the research on DNA PK as a target for increasing therapy, and discloses that DNAPK could be an ideal target for cancer therapy, but there are still many problems to be re solved in clinical applications.