Treatment efficiency of a suicide gene therapy using prostate-specific membrane antigen promoter/enhancer in a castrated mouse model of prostate cancer.
Suicide gene therapy has potential for the treatment of prostate cancer under conditions of androgen deprivation. We show here that the combination of promoter/enhancer of prostate-specific membrane antigen (PEPM) and the Cre-loxP system is a good method to express a suicide gene, namely herpes virus thymidine kinase (TK), in prostate cancer cells. We have examined this system in a castration model in vivo, in comparison with a prostate-specific antigen promoter/enhancer system (PP). In the castrated mice, the tumor luciferase activity with the combination of the PEPM plus the Cre-loxP system was about 50 times greater than that with the control GL3 plasmid. A similar increase was observed in non-castrated mice. In contrast, the luciferase activity of the plasmid PP was decreased significantly in tumors from castrated mice as compared with tumors from non-castrated control mice. Regarding the therapeutic effect, the combination plasmid PEPM-Cre plus CMV-loxP-TK exhibited a strong inhibitory effect on tumor growth in the castrated mice, as in the non-castrated mice. In contrast, PP-TK plasmid did not show any significant growth inhibition in the castrated mice. These findings indicate that the combination of PEPM and Cre-loxP system may have a good treatment effect under androgen ablation conditions in vivo, and our system may therefore be applicable to patients who have previously received androgen deprivation therapy.
Ikegami
Shusei
S
Department of Urology, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.
Tadakuma
Takushi
T
Ono
Takeshi
T
Suzuki
Satoshi
S
Yoshimura
Ichiro
I
Asano
Tomohiko
T
Hayakawa
Masamichi
M
D000230:Adenocarcinoma / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D017930:Genes, Reporter; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D043425:Glutamate Carboxypeptidase II / Q000235:genetics*; D018259:Herpesvirus 1, Human / Q000235:genetics; D006801:Humans; D008081:Liposomes; D008156:Luciferases / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009919:Orchiectomy; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000628:therapy*; D013937:Thymidine Kinase / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
D000954:Antigens, Surface; D008081:Liposomes; D008156:Luciferases; D013937:Thymidine Kinase; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II