FIGURE 6 from Pharmacologic Targeting of Histone H3K27 Acetylation/BRD4-dependent Induction of ALDH1A3 for Early-phase Drug Tolerance of Gastric Cancer

Combined effect of 5-FU and OTX015 on tumor growth in vivo.A, Experimental design of combination therapy with 5-FU and OTX015 in xenografted mice. JSC15-3 cells were subcutaneously injected into nude mice. After 7 days, mice were injected intraperitoneally with 100 mg/kg 5-FU at days 0, 7, and 14 and treated orally with 100 mg/kg OTX015 at days 7–11, 14–18, and 21 or both drugs. B, Tumor volume (top) and mouse body weight (bottom). Error bars represent the SD. ***, P < 0.001; ****, P < 0.0001, one-way ANOVA. C, Average tumor volume on day 21. N = 6; ***, P < 0.001, one-way ANOVA. D, IHC of Ki-67. Images are representative of five biological replicates. E, Quantitative data of D. IHC of ALDH1A3 (F) and its quantitative data (G). ***, P < 0.001; ****, P < 0.0001, one-way ANOVA. H, Schematic view of anticancer drug-induced ALDH1A3 expression in DTP cells in H3K27ac- and BRD4-dependent manners. TSS: transcription start site.