New sensitive discovery histoculture model for growth-inhibition studies in prostate cancer and BPH.

Background: A new, total-immersion three-dimensional histoculture (TIH) method was developed to evaluate growth of tissue containing a mixture of benign prostate hyperplasia (BPH) and prostate cancer in vitro.

Methods: Efficacy of inhibitors, such as genistein, was determined by measuring 3H-thymidine incorporation per microgram protein. Inhibitory effects obtained in TIH were compared to those in sponge-gel supported histoculture (SSH).

Results: 3H-thymidine incorporation was 2-5-fold higher in tissue cultured in TIH than in SSH. The average inhibition by genistein at a concentration of 18 JIM was 73% in TIH, vs. 31% in SSH. TIH also appeared to be more sensitive, since the lowest concentration of genistein that significantly inhibited growth of BPH mixed with prostate cancer tissue was 2.3 IJM, while in SSH the lowest concentration was 9.2 F,M. Although the within-assay coefficient of variation (CV) was similar for both TIH and SSH, the between-assay CV was better in TIH.

Conclusions: These data suggest that TIH can be used as a discovery model for screening and evaluating inhibitors of prostate tissue growth in vitro.