Synergistic effect of PARP inhibitor and BRD4 inhibitor in multiple models of ovarian cancer.

ABSTRACT: Ovarian cancer has the highest facility rate among gynaecological tumours. Current therapies including PARP inhibitors have a defect that ovarian tumour is easy to recurrent and become resistant to therapy. To solve this problem, we found that BRD4 inhibitor AZD5153 and PARP inhibitor olaparib had a widespread synergistic effect in multiple models with different gene backgrounds. AZD5153 sensitizes cells to olaparib and reverses the acquired resistance by down-regulating PTEN expression levels to destabilize hereditary materials. In this study, we used the following multiple ovarian cancer models PDX, PDO and 3D/2D cell lines to elucidate the co-effect of AZD5153 and olaparib in vivo and in vitro. The similar results of these models further proved that the mechanism identified was consiste

SUBMITTER: Huang Y 

PROVIDER: S-EPMC9983312 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature