Login to Access Video or Poster Abstract: 1615
Date & Time: May 17, 2011 10:30 AM
Session Title: Prostate Cancer: Basic Research
Sources of Funding: Source of Funding: Niels V. Johnsen supported by the SMSNA Scholars in Sexuality Research Grants Program, SMSNA; Tadalafil provided by Eli Lilly and Company

INTRODUCTION AND OBJECTIVES:
Erectile dysfunction (ED) following radical prostatectomy (RP) is commonly managed postoperatively with long?term phosphodiesterase type 5 (PDE5) inhibitors. The aim of this study was to examine the growth modulatory effect of tadalafil on various prostate cancer (PC) cell lines cultured in vitro.

METHODS:
Determination of drug concentrations was based on previously published data on steady?state plasma levels occurring with once daily 20mg dosing. Three androgen-independent PC lines, DU?145, PC?3 and C4?2B, were cultured at varying concentrations of purified tadalafil (1.5 x 10?3 mM to 1.5 x 10?9 mM) and cell proliferation was assessed using the WST?8 cell counting kit at 24, 48, and 72 hrs.

RESULTS:
PC-3 cells showed significant decreases in growth at 24 hours in 1.5 x 10-3 mM to 1.5 x 10-9 mM treatment groups, at 48 hours in the 1.5 x 10-3 mM, 1.5 x 10-4 mM, 1.5 x 10-6 mM, and 1.5 x 10-9 mM treatment groups, and at 72 hours in the 1.5 x 10-3 mM and 1.5 x 10-4 mM treatment group (p<0.05). DU-145 cells showed a significant dose-dependent decrease in cell growth at 24 hours in the 1.5 x 10-3 mM to 1.5 x 10-8 mM treatment groups, as well as at 48 hours in the 1.5 x 10-3 mM to 1.5 x 10-6 mM treatment groups and at 72 hours in the 1.5 x 10-3 mM treatment group (p<0.05). DU-145 cells did also show a time-dependent inhibition of growth over the first 48 hours at doses of 1.5 x 10-3 mM to 1.5 x 10-6 mM, with an average decrease in growth of 11.8% relative to control. C4-2B cells showed a decrease in cell growth of statistical significance (p<0.05) at 24 hours in the 1.5 x 10-4 mM and 1.5 x 10-5 mM treatment groups, and at 48 hours in the 1.5 x 10-3 mM to 1.5 x 10-7 mM treatment groups, as well as in the 1.5 x 10-9 mM group. C4-2B cells did not show a statistically significant growth inhibition at 72 hours at any tadalafil concentration tested. Time-dependent inhibition of growth, however, was also seen over the first 48 hours in the C4-2B line at doses of 1.5 x 10-3 mM to 1.5 x 10-7 mM, with a mean decrease in growth relative to control of 16.3%.

CONCLUSIONS:
Once daily dosing of 20mg tadalafil attains a steady?state concentration that is within the treatment range shown to decrease PC cell growth. Though 20mg dosing is rare, this preliminary study suggests that routine administration of tadalafil for ED may prove to have the additional benefit of inhibiting residual metastatic PC cell growth after RP, even at plasma concentrations attained with lower daily doses. Further studies are needed to examine the growth modulatory effect in normal prostate and androgen-dependent cancer cells, as well as to elucidate the mechanism of growth inhibition involved.

Authors

Johnsen, Niels; Ma, Limin; Abdel-Mageed, Asim; Hellstrom, Wayne