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论文摘要

阿柔比星降低米托蒽醌引起的细胞死亡的机制

Study on the mechanism of Aclarubicin reducing Mitoxantrone-induced cell death

作者:毛嘉(四川大学生命科学学院);周文娟(四川大学生命科学学院);潘洋(四川大学生命科学学院);刘岩(四川大学生命科学学院)

Author:MAO Jia(College of Life Sciences, Sichuan University);ZHOU Wen-Juan(College of Life Sciences ,Sichuan University);PAN Yang(College of Life Sciences, Sichuan University);LIU Yan(College of Life Sciences ,Sichuan University)

收稿日期:2019-03-29          年卷(期)页码:2020,57(1):186-190

期刊名称:四川大学学报: 自然科学版

Journal Name:Journal of Sichuan University (Natural Science Edition)

关键字:阿柔比星; 米托蒽醌; TOP2-DNA复合物; DNA损伤

Key words:Aclarubincin; Mitoxantrone; TOP2-DNA complexes; DNA damage

基金项目:国家自然科学基金(81872447)

中文摘要

为了研究阿柔比星(Aclarubicin , 简称ACL)和米托蒽醌(Mitoxantrone,简称MTX)联合作用的效果,采用细胞存活率试剂盒和Annexin V/PI双染检测两种药物对L929细胞存活率的影响,结果显示,ACL能降低MTX引起的细胞死亡.体内酶复合物检测结果显示,MTX显著地促进了拓扑异构酶2(TOP2) DNA复合物形成,而ACL可以极大程度地降低该复合物的水平.Western blotting结果表明,相比于MTX处理组细胞,ACL和MTX联用能够显著降低γH2AX蛋白的形成,说明ACL能降低MTX造成的DNA损伤.由此表明,ACL是通过阻止 TOP2 DNA复合物的形成来降低MTX引起的细胞死亡,并暗示了联合使用时ACL可能会对MTX有拮抗作用.

英文摘要

To explore the effect of Aclarubicin (ACL) and Mitoxantrone (MTX) combination, we detected the effects of the two drugs on the survival rate of the L929 cell line by cell survival kit and Annexin V/PI double staining. The results showed that ACL reduced MTX induced cell death. In vivo complex of enzyme assay (ICE assay) showed that MTX significantly promoted the formation of TOP2-DNA complexes, but ACL significantly reduced the level of this complex. Western blotting showed that compared with MTX treated cells, the combination of ACL and MTX can significantly reduce the formation of γH2AX protein, indicating that ACL can reduce MTX-induced DNA damage. This suggests that ACL countered MTX induced cell death via reducing TOP2-DNA formation, implicating that ACL might play an antagonistic role against MTX.

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