Figure 2.
The interaction of olaparib with MG18L and G47Δ in killing poly(ADP-ribose) polymerase inhibitor (PARPi)–sensitive and –resistant glioblastoma stem cells (GSCs). A) Dose response curves for MG18L (left) and G47Δ (right) in the indicated GSCs, determined as in Figure 1A. Combination of olaparib and MG18L or G47Δ in MGG4 (B), MGG23 (C), BT74 (D), MGG24 (E), and normal astrocytes (F). Left: The fixed dose of MG18L was MOI = 0.04, 0.001, 0.05, and 0.05 for (B), (C), (D), and (E), respectively, indicated with blue arrow. Middle: The fixed dose of olaparib was 1, 1, 10, and 10 µM for (B), (C), (D), and (E), respectively, indicated with brown arrow. Right: B and C) Interaction between olaparib (Ola) and MG18L or G47Δ in MGG4 and MGG23, as determined by the Chou-Talalay median effect method (19,40). Combination index < 1, = 1, and > 1 indicates synergistic, additive, and antagonistic interactions, respectively. Right: D and E) Combination of olaparib and G47Δ in BT74 (Ola = 10 μM) and MGG24 (Ola = 5 μM). Increasing virus dose is statistically significantly different from the previous dose, with or without olaparib (P < .0001). *P = .004; †P < .001; ‡P < .0001 (multiple comparisons test, Tukey). F) Combination of olaparib (10 μM, Ola (+)) and MG18L or G47Δ (0.1 MOI) in astrocytes. Cell viability was determined by MTS assay after six-day treatment and represented as mean ± SD. All statistical tests were two-sided. MOI = multiplicity of infection; Ola = olaparib; PARP = poly(ADP-ribose) polymerase.