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. Author manuscript; available in PMC: 2018 Jun 27.
Published in final edited form as: Clin Cancer Res. 2013 Aug 13;19(20):5658–5674. doi: 10.1158/1078-0432.CCR-13-0422

Figure 3. AZD1480 inhibits both primary and castrate-resistant prostate cancer xenograft tumor growth. (A) AZD1480 inhibits growth of s.c. and orthotopic CWR22Rv1 tumors.

Figure 3

Figure 3

Figure 3

CWR22Rv1 PC cells were inoculated s.c. (left panel) or orthotopically into prostates (right panel) of SCID mice. The mice were treated daily with AZD1480 (10 and 30 mg/kg) or vehicle as control administered by oral gavage. Tumor sizes were measured every 3 days, and the tumor volumes were calculated using the formula 0.5 × (larger diameter) × (smaller diameter) 2. (B) AZD1480 inhibits Stat5a/b activation in CWR22Rv1 tumors. Immunoblotting of tumor (s.c.) cell lysates with anti-pYStat5a/b mAb 2 or 24 h after administration of AZD1480 (30 mg/kg) to the mice (upper panel). Immunohistochemical detection of nuclear Stat5a/b in CWR22Rv1 tumors following 11 days of dosing at the indicated doses of AZD1480 demonstrates a decrease in the percentage of Stat5a/b-positive tumor cells. (C) AZD1480 inhibits both primary androgen-dependent growth of CWR22Pc tumors and castrate-resistant growth of recurrent CWR22Pc tumors after androgen deprivation-induced tumor regression. CWR22Pc cells were inoculated s.c. into the flanks of castrated athymic nude mice supplied with sustained-release DHT-pellets (n=10/treatment group, 1 tumor/mouse, 1.5 × 107 CWR22Pc cells/site). In treatment window (TW) 1 (primary androgen-sensitive PC growth) (left panels), mice were treated daily with vehicle, AZD1480 at 30 mg/kg or bicalutamide at 50 mg/kg for 21 days starting on day 12 by oral gavage. Tumor sizes were measured three times per week. In TWs 2 (middle panels) and 3 (right panels) (castrate-resistant PC growth), the DHT pellets were removed on day 32, and three days after DHT pellet removal, the mice were randomly distributed into three groups. Thirteen days (for TW 2) or 23 days (for TW 3) after DHT removal, treatment of the mice started with AZD1480 at 30 mg/kg or vehicle by oral gavage daily, or docetaxel at 5 mg/kg body weight once a week intravenously. Tumor growth rates were calculated for each treatment group and the fold changes in tumor volume (volume at timepoint/volume at treatment start) for each group are presented. (D) Kaplan-Meier analyses indicate that overall survival of AZD1480-treated mice is longer than docetaxel-treated mice in TWs 2 and 3.