Fig. 5: ENZ-resistant CRPC cells are sensitive to BET and CBP/p300 inhibitors in vitro and in vivo.

a Heatmap shows the sensitivity of C4-2^CON and C4-2^ENZ-R cells to the indicated pathway inhibitors. b Cell proliferation analysis shows the inhibitory effect of BET-CPB/p300 dual inhibitors NEO1132 and NEO2734 on C4-2^CON and C4-2^ENZ-R cell proliferation. Data shown as means ± s.d. (n = 3 replicates/group). Statistical significance was determined by two-way ANOVA. c Cell proliferation analysis of control and ENZ-R LNCaP, VCaP, and LAPC4 cells treated with the indicated concentration of NEO2734. Data shown as means ± s.d. (n = 6 replicates/group). Statistical significance was determined by two-way ANOVA. d Western blot analysis of AR, CXXC5, ID1, ID3, PFN2, TET2, BRD4, and p300 in C4-2^CON and C4-2^ENZ-R cells treated with NEO2734 at the indicated concentrations. ERK2 was used as a loading control; Experiments were repeated twice. e–g Effect of the indicated inhibitors on C4-2^ENZ-R xenograft tumor volume and weight. Data are represented as means ± s.d. (n = 10 replicates/group). Statistical significance was determined by two-way ANOVA for tumor volume and by unpaired two-tailed Student’s t tests for tumor weight. h Effect of the indicated inhibitors on mouse body weight. Data shown as means ± s.d. (n = 10 replicates/group). i IHC of AR, CXXC5, ID1, PFN2, Ki-67, and cleaved-caspase3 in tumors treated for 28 days with vehicle, ENZ, or NEO2734. Representative images (scale bar, 100 μm) and quantified data are shown in upper and lower panels, respectively. Data shown as means ± s.d. (n = 5 replicates/group). Statistical significance was determined by unpaired two-tailed Student’s t tests.