Figure 6

LuCaP 136 tumors treated with ganetespib have decreased PI3K and AR protein expression and show enhanced sensitivity to castration in vivo. (A) Tumor volume for LuCaP 136 treated with ganetespib (150 mg/kg, n = 8) or DMSO (n = 8) (P < 0.0005, two way anova with Bonferroni Corrections). (B) Western blots for the indicated biomarkers in individual tumors harvested 24 or 48 hours after ganetespib (G) treatment. Control and ganetespib treated samples were run on same gel but cropped during analysis for convenient visualization. (C) Representative H&E and cleaved caspase-3 IHC staining of LuCaP 136 tumors exposed to DMSO or 125 mg/kg ganetespib (G) for 24 or 48 hours (scale bars = 200 μm). (D) Waterfall plot showing individual tumor volumes at the greatest depth of ganetespib + castration PDX tumor response (4 week treatment) normalized to starting tumor volumes (Percent Relative Baseline). (E) LuCaP 136 tumor volumes for an untreated (n = 9) cohort or cohorts treated with castration (n = 10), ganetespib (125 mg/kg, n = 10), and ganetespib + castration (125 mg/kg, n = 9) (P < 0.005, 2-way anova with Bonferroni Corrections). All tumor measurements were averaged within respective cohorts and presented as averaged tumor volume +/− SEM. Data points are marked (X) to indicate the time at which individual mice were sacrificed after reaching the maximum allowed tumor size.