Objective:To investigate the in vitro the anti-prostate cancer effect of a novel polypeptide,APP216,so as to provide a basis for development of new drug for treatment of prostate cancer.Methods:The polypeptide drug included the amino sequences of BH3,K237 and DG2 domain and the peptide that could be digested by PSA.The anti-prostate cancer effects of the polypeptide prodrug on prostate cancer cell line LNCaP,22RV1(secreting PSA)and PC3,DU145(secreting no PSA)were determined by MTT test and Hoechst 33258 staining.Results:MTT test revealed that the surviving rates of LNCaP and 22PV1 cells were respectively 22% and 34% 48 h after APP216(270 ?g/ml)treatment,and 9.8% and 8.2% 72 h after APP216(270 ?g/ml)treatment.The surviving rates of PC3 and DU145 cells were respectively 90% and 95% 48 h after APP216(270 ?g/ml)treatment,and 87% and 92% 72 h after APP216(270 ?g/ml)treatment.Hoechst 33258 staining showed the typical features of cell apoptosis:cell shrinkage,chromatin condensation and hypodiploid genomic DNA content in LNCaP and PC3m cells.Flow cytometry showed an apotosis rate of 36.26% 48 h after APP216(270 ?g/ml)treatment in LNCaP cells,and of 1.63% after 48 h APP216(270 ?g/ml)treatment in PC3m cells.Conclusion:APP216 has a satisfactory in vitro cytotoxicity on human PSA-secreting prostate cancer cells and can induce tumor cell apoptosis,but not on non-PSA secreting prostate cancer cells,indicating APP216 polypeptide can be specifically digested by endonuclease enzyme.Meanwhile,BH3 domain can be transferred into cells and induce apoptosis through HIV-TAT.