Inhibition of NF-κB restores sensitivity to PLX51107 in BETi-resistant cells. A, NF-κB luciferase reporter gene assay of parental and resistant cells after treatment with PLX51107 (0.5 μmmol/L), PTL (1 μmmol/L), and the combination for 24 hours. B, The combination PLX55107 + PTL is synergistic (CI < 1). Each point represents a different combination of drug concentrations. C, Quantification of apoptotic cells for the experiments shown inþSupplementary Fig. S7. #, P < 0.05;*, P < 0.001.D and E, Parental and resistant 92.1 and Omm1.3 cells were analyzed by immunoblotting for the indicated proteins after 48-hour treatments with 0.5 μmmol/L PLX51107, 1 μmmol/L PTL, and the combination. The concurrent inhibition of BET and NF-κB reduces the expression of p-p65, p50, and CEBPD, while inducing PARP cleavage.