DNA Double-Strand Break Repair Inhibitors: YU238259, A12B4C3 and DDRI-18 Overcome the Cisplatin Resistance in Human Ovarian Cancer Cells, but Not under Hypoxia Conditions.

ABSTRACT: Cisplatin (CDDP) is the cornerstone of standard treatment for ovarian cancer. However, the resistance of ovarian cancer cells to CDDP leads to an inevitable recurrence. One of the strategies to overcome resistance to CDDP is the combined treatment of ovarian cancer with CDDP and etoposide (VP-16), although this strategy is not always effective. This article presents a new approach to sensitize CDDP-resistant human ovarian carcinoma cells to combined treatment with CDDP and VP-16. To replicate the tumor conditions of cancers, we performed analysis under hypoxia conditions. Since CDDP and VP-16 induce DNA double-strand breaks (DSB), we introduce DSB repair inhibitors to the treatment scheme. We used novel HRR and NHEJ inhibitors: YU238259 inhibits the HRR pathway, and DDRI-18 and A12B4C3 act

SUBMITTER: Macieja A 

PROVIDER: S-EPMC10605129 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature