Dual targeting of Bcl-xL and Mcl-1 leads to synergistic decreases in cell viability in 3D LNCaP95 spheroids and the LuCaP 167CR organoid model. Dual treatment of navitoclax and A-1331852 with S63845 in 3D prostate cancer models. A, Representative images for each treatment condition before treatment and 24, 48, and 72 hours after treatment. B and C, Viability of spheroids measured by 3D CellTiter-Glo after 72 hours of treatment. Plots show mean ± SD. ****, P D–F) or navitoclax and S63845 (G–I). Drug curves (D and G) show mean ± SD. Dose–response matrices (E and H) and Bliss synergy plots (F and I) were generated using the Synergyfinder+ R package to evaluate synergy. All spheroid experiments were completed in triplicate. Organoid experiments had six technical replicates with three biological replicates.
Brim et al. (Thu,) studied this question.