Aim:To evaluate the antiproliferative activity of contragestazol (DL111-IT) on the human prostate cancer cell linePC3 in vitro and in vivo and to elucidate its potential molecular mechanisms.Methods:The cell killing ability ofDL111-IT was measured by the 3-(4,5-dimethylthia-zol,2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent assaymethod and the tumor xenograft model.The cell cycle was analyzed by flow cytometry and protein expression,including retinoblastoma (pRb),cyclin-dependent kinase 4 (CDK4) and cyclin D1,was detected by Western blotting.Results:DL111-IT exhibited high efficiency on cell growth inhibition of the human androgen-independent prostatecancer cell line PC3.The drug concentration that yielded 50 % cell inhibition (IC_(50) value) was 9.9 mg/mL.In the PC3tumor xenograft study,DL111-IT (1.25 mg/kg-20.0 mg/kg) given once a day for 10 days significantly inhibited tumorgrowth,with the inhibition rate ranging from 21% to 50 %.Flow cytometric analysis indicated that DL111-IT couldcause G_1 arrest in the PC3 cell line,but not apoptosis.DL111-IT enhanced pRb expression and down-regulated CDK4and cyclin D1 expression,suggesting that cell cycle regulation might contribute to the anticancer property of DL111-IT.Conclusion:DL111-IT inhibits the proliferation of human androgen-independent prostate cancer cell line PC3 invitro and in vivo by a cell cycle regulation pathway.(Asian J Androl 2005 Dec;7:389-393) Aim: To evaluate the antiproliferative activity of contragestazol (DL111-IT) on the human prostate cancer cell line PC3 in vitro and in vivo and to elucidate its potential molecular mechanisms. Methods: The cell killing ability of DL111-IT was measured by the 3- 4,5-dimethylthia-zol, 2-yl) -2,5-diphenyltetrazolium bromide (MTT) reagent assay method and the tumor xenograft model. The cell cycle was analyzed by flow cytometry and protein expression, including retinoblastoma (pRb) dependent kinase 4 (CDK4) and cyclin D1, was detected by Western blotting. Results: DL111-IT exhibited high cell on cell growth inhibition of the human androgen-independent prostate cancer cell line PC3. The drug concentration that yielded 50% cell inhibition (IC_ (50) value) was 9.9 mg / mL.In the PC3 tumor xenograft study, DL111-IT (1.25 mg / kg-20.0 mg / kg) given once a day for 10 days significantly inhibited tumorgrowth, with the inhibition rate ranging ranging from 21% to 50%. Flow cytometric analysis showed that DL111-IT suggesting that the cell cycle regulation might contribute to the anticancer property of DL111-IT.Conclusion: DL111-IT inhibits the proliferation of human androgen-independent prostate cancer cell line PC3 invitro and in vivo by a cell cycle regulation pathway. (Asian J Androl 2005 Dec; 7: 389-393)