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

Figure 1. Pharmacodynamic activity of ISIS581088 in mouse prostate tumors.

Figure 1

(A) Conditional Pten-KO (18–19 weeks of age, n = 3–4 mice/group) mice received ISIS581088 (40 mg/kg i.p.) or the control ASO (40 mg/kg i.p.) as indicated. (B) Semiquantitative analysis and representative IHC images of ASO uptake in mPIN lesions of the dorsal (DP) and ventral (VP) lobes of mouse prostate. Cumulative distribution of the ASO was assessed according to distribution patterns against an antibody targeting the Generation-2.5 ASO backbone (np, not present; –, negative; +/–, slight; +, minimal; ++, moderate; n = 2–4 mice/group) Scale bars: 100 μm. (C) Ar mRNA expression analysis by qPCR. Horizontal bars represent ± SEM, and diamonds represent individual samples. Significance represent Student-Newman-Keuls post hoc test for individual comparisons, upon significant 1-way ANOVA (F4,22 = 5.301, P = 0.005). (D) AR protein expression by IHC. Scale bar: 50 μm. (E) Heatmap of AR protein, Ar mRNA, and AR target gene expression by qPCR in 20-week-old Pten-KO treated with ISIS581088 (ISI) or control ASO (Ctrl ASO) (n = 3–6 mice/group). (F) Correlation matrix of AR protein, Ar mRNA, and AR target gene expression; shaded squares represent P < 0.05.