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. 2022 Mar 8;12(3):730–751. doi: 10.1158/2159-8290.CD-21-0385

Figure 6.

Figure 6. JQAD1 causes tumor growth suppression and loss of EP300 in vivo. A, Kelly NB cell xenografts were established in NSG mice and mice treated with vehicle control (n = 9) or JQAD1 at 40 mg/kg i.p. daily (n = 10). Tumor growth curve kinetics were also analyzed by two-way ANOVA with mixed-effects analysis, demonstrating that JQAD1 suppresses tumor growth (P < 0.0001 for vehicle vs. JQAD1 treatment groups). B, Kaplan–Meier survival analysis of mice in A. JQAD1 prolongs survival (log-rank test P = 0.0003 for JQAD1-treated mice compared with vehicle). C, Normalized body weights of animals from A and B. D, IHC of EP300 and CBP in Kelly cell xenografts treated with either vehicle control or JQAD1 (40 mg/kg i.p. daily) for 14 days. Data are representative of three independent animals per treatment. Scale bar, 50 μm. E, ERCC spike-in RNA-seq was performed on tumor cells recovered from animals treated in D. Results are shown as the fold change in expression of animals treated with 40 mg/kg JQAD1 daily (n = 3) compared with vehicle control (n = 4) at day 14. RNA-seq groups of genes are stratified by their regulation by typical or super-enhancers and gene identity of TF or CRC gene. ***, P < 0.0001 between typical enhancer and super-enhancer groups and between typical enhancer and CRC gene expression; *, P = 0.0223 between super-enhancer groups and CRC gene expression; **, P = 0.0013 between all TFs and CRC gene expression. See also Supplementary Fig. S5.

JQAD1 causes tumor growth suppression and loss of EP300 in vivo. A, Kelly NB cell xenografts were established in NSG mice and mice treated with vehicle control (n = 9) or JQAD1 at 40 mg/kg i.p. daily (n = 10). Tumor growth curve kinetics were also analyzed by two-way ANOVA with mixed-effects analysis, demonstrating that JQAD1 suppresses tumor growth (P < 0.0001 for vehicle vs. JQAD1 treatment groups). B, Kaplan–Meier survival analysis of mice in A. JQAD1 prolongs survival (log-rank test P = 0.0003 for JQAD1-treated mice compared with vehicle). C, Normalized body weights of animals from A and B. D, IHC of EP300 and CBP in Kelly cell xenografts treated with either vehicle control or JQAD1 (40 mg/kg i.p. daily) for 14 days. Data are representative of three independent animals per treatment. Scale bar, 50 μm. E, ERCC spike-in RNA-seq was performed on tumor cells recovered from animals treated in D. Results are shown as the fold change in expression of animals treated with 40 mg/kg JQAD1 daily (n = 3) compared with vehicle control (n = 4) at day 14. RNA-seq groups of genes are stratified by their regulation by typical or super-enhancers and gene identity of TF or CRC gene. ***, P < 0.0001 between typical enhancer and super-enhancer groups and between typical enhancer and CRC gene expression; *, P = 0.0223 between super-enhancer groups and CRC gene expression; **, P = 0.0013 between all TFs and CRC gene expression. See also Supplementary Fig. S5.