In vitro and in vivo analysis shows eltanexor reduces tumor volume in colorectal cancer, indicating modulation of XPO1 impacts cell viability and signaling pathways.
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.)
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