LNCaP-RALR xenografts retain
biological resistance to
ralaniten and sensitivity to enzalutamide in vivo. (A) LNCaP and LNCaP-RALR tumor growth in castrated mice treated daily with ralaniten
(200 mg/kg), enzalutamide (10 mg/kg), or vehicle by oral gavage. Tumors
were harvested 2 days after last treatment. Data presented as mean
± SEM and analyzed by two-way ANOVA with Sidak’s test
applied post hoc. (B) Representative photographs
of LNCaP-RALR tumors. Scale bars: 10 mm. (C) Body weight
change over the course of the experiment. Data presented as mean ±
SEM and analyzed by two-way ANOVA with Dunnett’s test applied post hoc (n = 5 mice per group). (D) Representative
examples of immunohistochemistry (IHC) from LNCaP-RALR tumors
showing AR and PSA expression levels (n = 2 tumors
per group). (E) Real-time PCR of AR, FKBP5, RHOU, and PSA transcript normalized
to SDHA harvested from LNCaP-RALR tumors
(n = 8 tumors/sample for all genes except FKBP5, n = 6 for RAL). *p < 0.05; **p < 0.01; ***p < 0.001; #p < 0.0001; n.s., not
significant: RAL, ralaniten; ENZ, enzalutamide; VEH, vehicle.