奥拉帕尼
PARP抑制剂
氧化应激
同源重组
癌症研究
雷达51
DNA修复
DNA损伤
聚ADP核糖聚合酶
体外
氧化磷酸化
化学
分子生物学
DNA
生物
生物化学
聚合酶
作者
Qianqian Wu,Mingjing Wei,Lifang Yao,Xiaodong Cheng,Weiguo Lü,Xing Xie,Xiao Li
标识
DOI:10.1016/j.bbrc.2022.06.049
摘要
Tumors with homologous recombination (HR) deficiency are particularly responsive to PARP inhibitors, however strategies to improve the sensitivity of epithelial ovarian carcinoma (EOC) with sufficient HR abilities still need to be deeply explored. In the present study, we firstly validated that hyperthermia (HT) changed diverse genes and signal pathways related to HR and oxidative stress in HR proficient EOC cells. HT impaired HR efficiency through inhibiting Olaparib (Olap) induced RAD51 foci formation in EOC cells, which was independent of the expression level of RAD51. Combination therapy of HT and Olap synergistically induced oxidative stress and oxidative DNA damage of EOC cells. Furthermore, we revealed that HT and Olap synergistically aggravated double-strand breaks of DNA in EOC cells. Conclusively, our findings confirmed that HT could synergistically enhance HR proficient EOC cells' sensitivity to PARP inhibitor through impairing HR efficiency and increasing oxidative stress.
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