Fig. 3.

The PARP inhibitors rucaparib and talazoparib synergize with CNDAC in both BRCA1/2 proficient and deficient ovarian cancer cell lines. a BRCA1 deficient (− BRCA1) cells were exposed to rucaparib (30–250 nmol/L) 1 h before addition of CNDAC (3–25 nmol/L). b BRCA1 complemented (+ BRCA1) cells were exposed to rucaparib (1.2–3.5 μmol/L in Exp. 1, or 1– 3 μmol/L in Exp. 2) 1 h before addition of CNDAC (24–70 nmol/L in Exp.1, or 25–75 nmol/L in Exp.2). c BRCA2 deficient (− BRCA2) cells were exposed to rucaparib (5–200 nmol/L) 1 h before addition of CNDAC (5– 20 nmol/L). d BRCA2 revertant (BRCA2 rev.) cells were exposed to rucaparib (0.8–4 μmol/L) 1 h before addition of CNDAC (20–100 nmol/L). a–d 24 h after CNDAC addition, drugs were washed out and cells were incubated in medium with rucaparib at the corresponding concentrations until colonies were fixed. Top, representative of 2 independent experiments, comparison of clonogenicity of − BRCA1 cells after treatment with rucaparib alone versus rucaparib–CNDAC combination at a fixed ratio as indicated. Bottom, CIs from median-effect analysis of the 2 experiments are presented in the accompanying inserts. e BRCA2 deficient (− BRCA2) cells were exposed to talazoparib (0.4–1 nmol/L in Exp. 1 and 2, or 0.4–1.6 nmol/L in Exp. 3 and 4) 1 h before addition of CNDAC (4.8–12 nmol/L in Exp. 1 and 2, or 3.6–14.4 nmol/L in Exp. 3 and 4). f BRCA2 revertant (BRCA2 rev.) cells were exposed to talazoparib (10–60 nmol/L in Exp. 1 and 2, or 15–100 nmol/L in Exp. 3 and 4) 1 h before addition of CNDAC (16–96 nmol/L in Exp. 1 and 2, or 15–100 nmol/L in Exp. 3 and 4). e–f Drugs were washed out 24 h after CNDAC co-incubation, and cells were incubated in medium with talazoparib at the corresponding concentrations until colonies were fixed. Top, representative of four independent experiments, comparison of clonogenicity of BRCA2 deficient cells after treatment with talazoparib alone versus talazoparib–CNDAC combination at a fixed ratio as indicated. Bottom, CIs from median-effect analysis of the four experiments are presented in the accompanying inserts