Specific targeting of prostate cancer cells in vitro by the suicide gene|[sol]|prodrug system, uracil phosphoribosyltransferase|[sol]|5-fluorouracil, under the control of prostate-specific membrane antigen promoter|[sol]|enhancer

摘要

This study was designed to investigate the prostate cancer-specific tumoricidal effect of the suicide gene, Escherichia coli uracil phosphoribosyltransferase (UPRT), driven by the human prostate-specific membrane antigen promoter/enhancer (PSMAE/P) in vitro. When transfected with PSMAE/P-EGFP (enhanced green fluorescence protein) (a plasmid construct with the green fluorescence protein gene driven by the PSMAE/P), only the androgen-responsive and PSMA-positive prostate cancer cell line, LNCaP, expressed GFP, indicating the specificity of the PSMAE/P activity in androgen-sensitive and PSMA-positive prostate cancer cells. Taking advantage of this prostate cancer-specific property of PSMAE/P, we successfully introduced bacterial UPRT into LNCaP cells where the tumoricidal effect of 5-fluorouracil (5-FU) was significantly increased when compared with the cells without the exogenous UPRT. We conclude that the efficacy of 5-FU-based chemotherapy in prostate cancers can be significantly improved by targeted expression of the suicide gene UPRT under the control of PSMAE/P.