Figure 2. Potentiation of PARPi cytotoxicity with IRN and TMZ.
(A) Model of DNA damage and synthetic lethality for the combination of PARPis with TMZ or IRN. (B-D) Dose response for EW-8, ES-6, and SAOS cells 72 hours after exposure to each indicated PARPi. Curves fit using data pooled from two biological replicates, each with at least three technical replicates. (E) A similar experiment was performed at 144 hours. (F) Immunoblot with quantification (G) of the knock down of PARP1 in EW-8 cells transfected with a PARP1 siRNA. (H-J) Dose response for BMN-673, olaparib, and veliparib in EW-8 cells at 72 hours with (solid line) and without (dashed line) knock down of PARP1. Each data point is the mean ± SD of triplicate wells. (K-P) Potentiation of PARPi in the presence of increasing concentrations of TMZ and SN-38. Curves were generated by taking horizontal slices through the efficacy surface estimated using the response surface model (RSM) approach.