Eltanexor treatment reduces tumor burden and size in Apcmin/+ mice. A, Representative photo of Apcmin/+ mouse adenoma and adjacent normal colon IHC stained for XPO1. Nuclei are counterstained with hematoxylin. The “T” label on the tissue represents tumor tissue, and the “N” label represents normal tissue. The scale bars represent 200 μm. B, Seven mice received vehicle three times per week and seven mice received eltanexor three times per week at a dose of 10 mg/kg by oral gavage. Representative small intestine regions from Apcmin/+ mice that received vehicle or eltanexor treatment. The tissue was fixed with 10% formalin and stained with 0.1% methylene blue. The arrows point to tumors present on the tissue. C, Total intestinal tumor burden of Apcmin/+ mice that were treated from the age of 4 to 11 weeks with 10 mg/kg of eltanexor or vehicle 3×/week. The value represents the mean total intestinal tumor burden ± SEM of seven different mice. A Student t test was used to statistically compare tumor burden in vehicle-treated and eltanexor-treated mice. D, Frequency of ≤0.4 mm, 0.5 to 0.9 mm, and ≥1 mm tumors in the vehicle-treated and eltanexor-treated groups. E, Representative images and quantifications of vehicle-treated and eltanexor-treated tumors immunofluorescently stained for XPO1. Hoechst was used to stain the nucleus, and green represents the protein of interest. F, The quantifications are the mean fluorescent signal produced by an individual tumor. Three individual mice that received vehicle or eltanexor treatment were used in the quantification. The values represent the mean XPO1 fluorescence ± SEM. The scale bars represent 200 μm. A Student t test was used to statistically compare XPO1 protein expression in vehicle-treated and eltanexor-treated mice. G, Representative images and quantifications of vehicle-treated and eltanexor-treated tumors immunofluorescently stained for COX-2. Hoechst was used to stain the nucleus, and the green represents COX-2. H, The graph depicts the number of COX-2–positive cells per image. Three mice, vehicle treated or eltanexor treated, were used in the quantification. The scale bars represent 200 μm. A Student t test was used to statistically compare COX-2 protein expression in vehicle-treated and eltanexor-treated mice. A.U., arbitrary units. (*, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001.)
Evans et al. (Tue,) studied this question.
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