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人8羟-基鸟嘌呤DNA糖苷酶1基因低表达增加肺腺癌细胞对博来霉素的敏感性

Low expression of human 8-oxoguanine DNA glycosylase-1 gene increases sensitivity of human lung adenocarcinoma cells to bleomycin
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摘要 目的研究DNA碱基切除修复基因人8羟-基鸟嘌呤DNA糖苷酶1(hOGG1)低表达增加肺腺癌细胞对博来霉素(BLM)的敏感性的作用,为化疗增敏提供更多的实验依据。方法以肺腺癌A549细胞和通过稳定转染hOGG1核酶而获得的hOGG1低表达的A549-R细胞为研究对象,用MTT试验和集落形成抑制试验测定不同浓度BLM处理后两种细胞的存活率和形成集落的能力;体外微核试验及单细胞凝胶电泳检测两种细胞微核率及DNA损伤与修复的差异。结果BLM作用下A549-R细胞的IC50及集落形成率显著低于A549细胞;BLM可诱导两种细胞的微核率增高,而在相同浓度下A549-R细胞微核率较A549细胞更高;单细胞凝胶电泳结果显示,BLM作用下两种细胞均有不同程度DNA损伤,A549-R细胞的拖尾率和DNA迁移长度显著大于A549细胞;损伤后A549细胞修复发生较A549-R早,与A549细胞相比A549-R细胞更不易修复。结论hOGG1低表达使肺腺癌细胞DNA修复能力降低,从而使其对BLM的敏感性增强。 AIM To investigate the effect of low expression of human 8-oxoguanine DNA glycosylase (hOGG)1 gene on sensitivity of lung adenocarcinoma cells to bleomycin, and provide more experimental evidence of sensitizing the response of tumor to chemotherapy. METHODS Human lung adenocarcinoma A549 cells and A549-R cells into which ribozyme gene inhibited the hOGG1 mRNA expression and transfected were studied. The cell viability and the ability of colony forming after treatment of bleomycin of different concentrations detected by MTY test and colony forming inhibition test. Micronucleus rate, DNA damage and repair were detected by micronucleus test in vitro and single cell gel electrophoresis assay. RESULTS The cell viability after treatment of bleomycin was decreased, IC50 of bleomycin and the ability of colony forming was significantly lower in A549-R cells than in A549 cells. The micronucleus rate in A549-R cells was higher than A549 cells statistically. DNA damage of A549-R cells induced by bleomycin of different concentrations was more serious than A549 cells both in comet cell rate and DNA migration length. The DNA repair after treatment of bleomycin happened earlier in A549 cells than in A549-R cells. The repair capability in A549-R cells was significantly lower than A549 cells. CONCLUSION Down-regulation of the expression of hOGG1 can decrease the DNA repair capability of A549 cells, and increase the sensitivity of cells to bleomycin.
出处 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2006年第4期312-317,共6页 Chinese Journal of Pharmacology and Toxicology
基金 国家自然科学基金资助项目(30571535)~~
关键词 基因表达 人8-羟基鸟嘌呤DNA糖苷酶 博来霉素 腺癌 DNA损伤 gene expression human 8-ox-oguanine DNA glycosylase bleomycin adeno-carcinoma lung DNA damage
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