Eltanexor shows increased sensitivity to tumor-derived organoids compared with WT mouse small intestine organoids. A, Representative photos of Apcmin/+ tumor–derived (tumoroids) and WT mouse small intestinal tissue–derived organoids. B, Representative photos of WT organoids treated with 200 nmol/L eltanexor for 72 hours. C, Representative photos of tumoroids treated with 200 nmol/L eltanexor for 72 hours. D, Tumoroids and WT organoids were treated with a dosage of 200 nmol/L eltanexor over 72 hours. Every 24 hours, the relative change in the surface area of each population was determined in ImageJ. The relative change is normalized to each population’s average surface area at hour 0. Values represent the mean of three individual experiments ± SEM. At least 50 organoids were measured at each time point under each treatment condition. A Student t test was used to statistically compare relative changes in surface area at each time point between control-treat and eltanexor-treated groups. E, Representative photos of both organoid populations that were treated with 400 nmol/L eltanexor for 72 hours. After 72 hours, each population was stained with 10 μg/mL of Hoechst and 10 μg/mL of PI. The organoids experiencing cell death will stain with PI. F, Tumoroids and WT organoids were treated with DMSO or 50 nmol/L, 100 nmol/L, 200 nmol/L, 400 nmol/L, and 800 nmol/L eltanexor for 72 hours. At 72 hours, the organoids were stained with 10 μg/mL of Hoechst and 10 μg/mL of PI. The graph represents the percentage of organoids from each population that was stained with PI under the various eltanexor dosages. The values represent the mean of three individual experiments ± SEM. A Student t test was used to statistically compare % PI-positive organoids in each treatment group between control-treat and eltanexor-treated groups. (*, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001.)
Evans et al. (Tue,) studied this question.