Extended Data Fig. 11: AU-15330 inhibits CRPC growth and synergizes with the AR antagonist enzalutamide.
From: Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer
(a) Schematic outlining the AU-15330 in vivo efficacy study using the C4-2B (CRPC) xenograft model. C4-2B-xenograft bearing male mice were castrated and, upon tumor regrowth, randomized into various treatment arms. (b) Body weight measurements showing the effect of the indicated treatments on animal weight. Tumor-bearing SCID mice were treated with the indicated drug throughout the treatment period, and the body weight was measured at endpoint. Data are presented as mean +/− SEM (n = 10, biological replicates). (c) Individual tumor volumes from different treatment groups with p-values are shown (two-sided t-test). Data are presented as mean +/− SEM (n = 20, biological replicates). (d) Immunoblots of direct AU-15330 targets (SMARCA2, SMARCA4, and PBRM1) in the whole cell lysate from C4-2B xenografts from all treatment arms after 5 days of in vivo treatment (n = 4, biological replicates). Vinculin is the loading control probed on a representative immunoblot. (e-g) VCaP, C4-2B, and LNCaP cells were treated with AU-15330 and/or enzalutamide at varied concentrations to determine the effect on cell growth and drug synergism, with assessments using the Bliss Independence method. Red peaks in the 3D-plots denote synergy with the average synergy scores noted above. The mean of three biological replicates is shown on top. Data are presented as mean (n = 4) from one-of-three independent experiments. (h) Crystal violet staining showing the synergistic effect of AU-15330 and enzalutamide on colony formation in VCaP and LNCaP. (i, j) Dose–response curves of VCaP cells treated with enzalutamide in combination with DMSO or AU-15330 at indicated concentrations. Data are presented as mean +/− SD (n = 4) from one-of-three independent experiments. (k) Dose-response curves of VCaP_Parental and VCaP_EnzR cells treated with enzalutamide or AU-15330. Data are presented as mean +/− SD (n = 6) from one-of-three independent experiments. (l) IC50 for AU-15330 in enzalutamide-resistant (EnzR) LNCaP and VCaP cells after 5 days of treatment.
