期刊
ONCOTARGET
卷 8, 期 4, 页码 6319-6329出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.14062
关键词
HDAC; BRCA1; CHK1; RAD51; acute myeloid leukemia
资金
- National Natural Science Foundation of China [NSFC 31271477, NSFC 31471295]
- China Scholarship Council
- Hyundai Hope on Wheels
- LaFontaine Family/U Can-Cer Vive Foundation
- Kids Without Cancer
- Children's Hospital of Michigan Foundation
- Decerchio/Guisewite Family
- Justin's Gift
- Elana Fund
- Ginopolis/Karmanos Endowment
- Ring Screw Textron Endowed Chair for Pediatric Cancer Research
Resistance to chemotherapy and a high relapse rate highlight the importance of finding new therapeutic options for the treatment of acute myeloid leukemia (AML). Histone deacetylase (HDAC) inhibitors (HDACIs) are a promising class of drugs for the treatment of AML. HDACIs have limited single-agent clinical activities, but when combined with conventional or investigational drugs they have demonstrated favorable outcomes. Previous studies have shown that decreasing expression of important DNA damage repair proteins enhances standard chemotherapy drugs. In our recent studies, the pan-HDACI panobinostat has been shown to enhance conventional chemotherapy drugs cytarabine and daunorubicin in AML cells by decreasing the expression of BRCA1, CHK1, and RAD51. In this study, we utilized class-and isoform-specific HDACIs and shRNA knockdown of individual HDACs to determine which HDACs are responsible for decreased expression of BRCA1, CHK1, and RAD51 following pan-HDACI treatment in AML cells. We found that inhibition of both HDAC1 and HDAC2 was necessary to decrease the expression of BRCA1, CHK1, and RAD51, enhance cytarabine-or daunorubicin-induced DNA damage and apoptosis, and abrogate cytarabine-or daunorubicin-induced cell cycle checkpoint activation in AML cells. These findings may aid in the development of rationally designed drug combinations for the treatment of AML.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据