Eltanexor reduces XPO1 protein while reducing cell viability. A, Human colorectal cancer cell lines HCA7, HCT116, SW480, DLD-1, and RKO with varying concentrations of eltanexor. The cell survival was measured with CCK8 after incubation for 72 hours with eltanexor. The data represent the mean seven individual experiments ± SEM. The chart shows determined IC50 values. B, Phase-contrast images showing HCT116 cells treated with varying dosages of eltanexor for 48 hours. C and D, HCT116 WT cells were injected into each of the subcutaneous dorsal flanks of athymic nude mice (two tumors/mouse). Measurements were taken 3× a week. Values graphed represent mean tumor volume ± SEM. Mice were either treated with 10 mg/kg eltanexor or the vehicle 3×/week. Representative images of tumors from the vehicle-treated and eltanexor-treated mice (vehicle treated n = 2 mice; eltanexor treated n = 3 mice). A Student t test was performed to statistically compare the vehicle-treated tumor volume to the eltanexor-treated tumor volume. E, Fluorescent microscopy images of HCT116 cells treated with control or 200 nmol/L eltanexor for 48 hours. Green represents XPO1, and DAPI was used to stain the nucleus. The scale bars represent 25 μm. F, Comparison of XPO1 fluorescent signal between control-treated and 200 nmol/L eltanexor-treated cells. The values graphed are the mean fluorescence values of three independent experiments ± SEM. At least 40 cells were quantified for each experiment. A Student t test was used to statistically compare the control-treated group fluorescence to the eltanexor-treated group fluorescence. G, Immunofluorescent detection of XPO1 in the vehicle- and eltanexor-treated tumors. Green represents XPO1 and Hoechst was used to stain the nucleus. Representative tissue sections were used and imaged at 20× magnification. The scale bars represent 200 μm. H, Comparison of XPO1 fluorescent signal between vehicle-treated and eltanexor-treated tumors. The values graphed are the mean fluorescence value of three xenograft tumors ± SEM. A Student t test was used to statistically compare XPO1 fluorescence in vehicle-treated and eltanexor-treated tumors. A.U., arbitrary units. (*, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001.)
Evans et al. (Tue,) studied this question.
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