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. 2019 Sep 5;4(17):e122688. doi: 10.1172/jci.insight.122688

Figure 3. Antitumor activity of ISIS581088 in mouse Pten-deficient prostate tumors.

Figure 3

(A) Experimental design for drug intervention model. Mice were randomized into vehicle-treated (n = 8), control ASO (n = 6), or ISIS581088 (n = 12) cohorts, and mice 4 weeks after surgical castration (Orch, n = 8) are also shown. Control ASO and ISIS581088 were administered i.p. for 4 weeks (40 mg/kg/d for first week loading, followed by 3 weeks of maintenance dosing, 40 mg/kg 3×/week). Data represent the pooled analysis from 2 independent experiments using age-matched mice. (B) Representative images of genitourinary tracts (GUT). Prostate tumors are highlighted by a yellow mask; scale represents mm. (C) Plots of GUT weight; horizontal bars represent mean ± SEM, and diamonds represent individual samples. Significance represent Dunn’s post hoc test for individual comparisons, upon significant 1-way ANOVA on ranks (H3 = 25.632, P < 0.001). (D) Plots of prostate tumor area; horizontal bars represent mean ± SEM, and diamonds represent individual samples. Significance represent Student-Newman-Keuls post hoc test for individual comparisons, upon significant 1-way ANOVA (F3,30 = 82.965, P < 0.001). (E) Representative H&E-stained sections of mouse prostate tumors. Scale bars: 200 μm. (F) Plot of Ar mRNA expression determined by qPCR. Horizontal bars represent mean ± SEM, and diamonds represent individual samples. (G) Representative IHC photomicrographs of AR, the proliferation marker Ki67, and apoptosis marker cleaved caspase-3 in mouse prostate tumors. Plots represent percentage of positive-stained cells in epithelial cancer cells (n = 6 mice/group); horizontal bars represent mean ± SEM, and diamonds represent individual samples. Significance represent Student-Newman-Keuls post hoc test for individual comparisons, upon significant 1-way ANOVA (Ki67, F3,19 = 28.843, P < 0.001; c. casp-3, F3,19 = 16.276, P < 0.001). Scale bars: 100 μm. (H) Confirmation of AR inhibition and apoptosis induction by Western blot expression of AR, cleaved caspase-3. GAPDH was used a loading control.