Hyperthermia synergistically enhances antitumor efficacy of PARP inhibitor through impacting homologous recombination repair and oxidative stress in vitro

Abstract

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.