Fig. 4.

PDE5 inhibition attenuates CRPC by interfering with myofibroblast activation. (A and B) Tumors were established in 6-wk-old FVB/N males (n = 10), as described earlier. Sildenafil was either added or not to the drinking water (0.7 g/L). (A) Tumor volume was measured every 2–3 d. Results are averages ± SEM. (B) Tumors were collected 1 wk after castration and analyzed for SMA by IHC. The areas occupied by SMA⁺ cells were determined as described earlier (n = 2). (C) Tumor-associated fibroblasts were purified from mice bearing Myc-CaP tumors and incubated in either a standard incubator or an hypoxic chamber (1% O₂) for 24 h in the absence or presence of indicated inhibitors. CT, control; H, hypoxia; PTX, pentoxyfidine; SILD, sildenafil. Expression of the indicated mRNAs was analyzed by Q-PCR as described earlier (n = 5). Results are averages ± SD.