Figure 7. Abiraterone and Plk1 inhibitors synergize in vivo and cause enhanced mitotic arrest in a murine PDX model of CRPC.

(A) Castrated male mice carrying LVCaP-2CR PDXs were administered the indicated drugs. Each tumor’s volume was normalized to day 0. Mean ± SEM where n ≥ 6; *, **, and *** indicate p ≤ 0.05, 0.01, and 0.001, respectively, relative to vehicle control using Tukey’s multiple comparisons test.

(B) Drug combination interaction indices according to (65) where values < 0 indicate synergy. * p ≤ 0.05 and ** p ≤ 0.01, using a bootstrap-t method with 10,000 random samples.

(C) End-of-study tumors were fixed and sections were stained with DAPI (blue) and anti-pHH3 antibodies (green). Scale bar bottom right 20 μm.

(D) Examples of mitotic figures in tumor sections stained with DAPI (blue). Bottom micrographs include pHH3 staining (green). Scale bar bottom right 5 μm.

(E) Quantification of pHH3+/mitotic cells in tissue sections. Plotted is the mean ± SEM, n ≥ 6 tumors per condition and ≥ 6724 cells per tumor. Data from individual tumors are overlaid as circles. P values were calculated using a Student’s two-tailed t-test; n.s. not significant.