Figure 3.

In vivo efficacy of CCT241736 in MOLM-13 human tumor xenografts. (A) Athymic mice (8 per cohort) were injected subcutaneously with 2 × 10⁶ MOLM-13 cells. Five days after implantation, mean tumor diameter was 6 mm (day 0 on graph), and dosing began orally twice per day with vehicle, 25, 50, or 100 mg/kg. Tumor volumes were measured at days 0, 3, 5, 7, 10, and 12. Mean tumor volumes ± SEM are shown. Unpaired Student t test of 95% confidence intervals on day 7. ns, not significantly different (P = .14; control: CCT241736 at 25 mg/kg). **P = .08 (control: CCT241736 at 50 mg/kg); ****P < .0001 (control: CCT241736 at 100 mg/kg). (B) Biomarker modulation by CCT241736 in MOLM13 xenograft samples. Tumors were removed 2 hours after the final dose, and lysates were prepared. Equal amount of proteins from all the tumors were analyzed by immunoblotting using the indicated antibodies for P-STAT5 and Aurora signaling (P-Aurora A, survivin). GAPDH was used as loading control. (C) CCT241736 induces aberrant mitosis in MV4-11 xenograft tumors. Tumors from mice treated with 100 mg/kg CCT241736 for 18 days (orally twice per day) were removed 2 hours after the final dose and analyzed by immunofluorescence using α-tubulin (green) antibodies and DAPI (blue) (40× magnification). (D) Quantification of mitotic cells. At least 50 mitotic cells in control and treated tumors were counted for bipolar or aberrant mitosis.