Fig. 4

The combination of ceritinib and enzaluamide has greater effects on tumor-inhibition activity of LAR TNBCs. (A) The activation of androgen-dependent AR signaling compensated the inhibition of androgen-independent AR signaling pathways by ceritinib. MDA-MB 453 cells grew in DMEM with 10% FBS. The cells were treated with DMSO, 10 μM ceritinib, 100 nM DHT, and 10 μM ceritinib with 100 nM DHT for 8 h. The poteins were detected by WB assay. The combination of ceritinib and enzaluamide showed synergistic effects in killing MDA-MB 453 (B) and SUM185PE cells (C). SUM159PT SCID mouse xenografts. Mice were divided into four groups randomly, (1) untreated control, (2) ceritinib (50 mg/kg bodyweight) alone, (3) enzaluamide alone (25 mg/kg of bodyweight), and (4) ceritinib (50 mg/kg bodyweight) + enzaluamide (25 mg/kg of bodyweight). Ceritinib or enzaluamide alone showed modest inhibition of tumor growth. However, the combination of ceritinib and enzaluamide robust suppression of tumor progression. (E) Proposed mechanism of the dual blockade of AR signaling pathways through the combination treatment of enzalutamide and ceritinib. AR signaling pathways include an androgen-dependent canonical signaling pathway and androgen-independent signaling pathways. The data represent mean ± SEM and are ananlyzed by GraphPad prism 8 software. * p < 0.05