PT - JOURNAL ARTICLE AU - CHENG, LIANG AU - ZHANG, SHAOBO AU - SWEENEY, CHRISTOPHER J. AU - KAO, CHINGHAI AU - GARDNER, THOMAS A AU - EBLE, JOHN N. TI - Androgen Withdrawal Inhibits Tumor Growth and Is Associated with Decrease in Angiogenesis and VEGF Expression in Androgen-Independent CWR22Rv1 Human Prostate Cancer Model DP - 2004 Jul 01 TA - Anticancer Research PG - 2135--2140 VI - 24 IP - 4 4099 - http://ar.iiarjournals.org/content/24/4/2135.short 4100 - http://ar.iiarjournals.org/content/24/4/2135.full SO - Anticancer Res2004 Jul 01; 24 AB - Recent evidence suggests that androgens stimulate growth of human prostate cancer partly by regulating expression of growth factors such as vascular endothelial growth factor (VEGF) in vitro and in vivo. In this study, we used CWR22Rv1, a novel androgen-responsive but androgen-independent human prostate cancer model, to evaluate the effect of androgen withdrawal on tumor growth, expression of VEGF and the cell proliferation marker Ki-67, and angiogenesis. A time-release testosterone pellet was implanted three days before inoculation of CWR22Rv1 cells in the mice. The tumor volumes were measured every three days. Serum PSA was measured on days 1, 12, 20, 27 and 34 post inoculation. Castration was performed on the 20th day post inoculation. Immunohistochemical assays were used to evaluate cell proliferation and microvessel density. Enzyme-linked immunosorbent assay (ELISA) was used to quantify VEGF expression. The average tumor volumes in the castration group on the 27th and 34th days were 122 and 168 mm3, respectively, compared to 156 and 210 mm3 in the noncastration group (p<0.01). Serum PSA level in the castration group decreased to about 41% of the level of the non-castration group (p<0.01). The VEGF protein levels in the tumors of castrated and non-castrated mice on day 34 were 0.62 pg and 1.36 pg/100 μg total protein, respectively (p<0.001). The mean percentage of Ki-67-positive tumor cells in the castrated and non-castrated groups were 1.8% and 2.8%, respectively (p=0.015). The mean microvessel densities in the castrated and non-castrated groups were 15 and 22 vessels/field, respectively (p<0.01) We conclude androgen withdrawal reduced both VEGF and microvessel density, and this was associated with decreased cellular proliferation in androgen-independent CWR22Rv1 human prostate cancer tumor in vivo. Copyright© 2004 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved