Figure 4.

Effects of SU086 on the growth of PDX models of prostate cancer in vivo and ex vivo prostate cancer specimens

(A) Schematic diagram of PDX models. Xenografts were generated by implantation of cultured LuCaP 147 or LuCaP 136 cells into the rear flank of immunocompromised NSG male mice (represented in red) concurrently with a testosterone pellet (represented in blue) in a remote subcutaneous implantation site. 5 × 10⁶ cells were implanted and grown for 1 month at which time the tumors were harvested, and fragments (20 mg) were serially passaged into mice (represented in purple) also implanted with testosterone pellets. Transplanted tumors were grown to 50 mm³ tumor volume on average prior to randomization and treatment initiation with 50 mg/kg SU086 or vehicle control (i.p. daily). Animal weights and tumor volumes (L × W × H/2) were measured every third day. At day 18 tumors were harvested.

(B and C) LuCaP 147 (B) and LuCaP 136 (C) tumor volumes are graphed as a fold change over day 0 ±SEM. Animals were sacrificed when the average tumor volumes of the vehicle-treated group reached 200 mm³ (LuCaP136) or 250 mm³ (LuCaP147). Accompanying histological analysis of subcutaneous xenografts and Ki67 staining was performed. The Ki67 proliferative index was quantified as percentage of positive nuclei per field, as an average of three fields, ±SD. Scale bars indicate 25 μm.

(D) Ex vivo culture of fresh primary human prostate cancer tissues in medium with vehicle or SU086 (5 μM), three slices per treatment. 8-mm tissue cores were extracted from radical prostatectomy samples. Precision-cut 300-μm tissues slices were cultured in a rotating apparatus for 72 h with medium and compound exchanged daily. Specimens were assayed by H&E and Ki67 staining as described above, and graphed ± SD. ∗p < 0.05, ∗∗p < 0.01; ns, no significance. Scale bars are 50 μm.