Adenovirus-mediated Suicide Gene Therapy for Experimental Prostate Cancers with in Vivo Tumor Transduction Using the Herpes Simplex Virus Thymidine Kinase Gene/Acyclovir System / 대한비뇨기과학회지
Korean Journal of Urology
;
: 985-991, 1999.
Artigo
em Coreano
| WPRIM
| ID: wpr-19852
ABSTRACT
PURPOSE:
The goal of this in vivo study is to determine the feasibility and efficacy of suicide gene therapy using adenovirus-mediated herpes simplex virus thymidine kinase (HSV-TK) and the prodrug acyclovir (ACV) system in animal model of human prostate cancer. MATERIALS ANDMETHODS:
We used a replication-defective adenoviral vector containing the beta-galactosidase gene (Ad-CMV-beta-gal) as a control and Adenovirus-Cytomegalovirus-Thymidine Kinase (Ad-CMV-TK) as the therapeutic vector under the trascriptional control of the CMV promoter. Transduction efficiency was assessed in vitro by infection of LNCaP and PC-3 human prostate cancer cells with Ad-CMV-beta-gal utilizing X-gal staining. TK activity in LNCaP and PC-3 cells infected with Ad-CMV-TK was determined by measuring the TK-mediated [3H]-Ganciclovir (GCV) phosphorylation. Sensitivity of LNCaP and PC-3 cells to Ad-CMV-TK in vitro was determined after infection of therapeutic vector with or without ACV. Subcutaneous tumors were established in athymic nude(nu/nu) mice with PC-3 cells, and Ad-CMV-TK/ACV sucide gene therapeutic system-induced inhibition of tumor growth in vivo was determined in separate and controlled experiments.RESULTS:
The mean TK activity was significantly higher in Ad-CMV-TK-infected LNCaP and PC-3 cells than in cells infected with Ad-CMV-beta-gal that was used as a control(P<0.05). The growth of human prostate cancer cells with Ad-CMV-TK was significantly inhibited by the addition of GCV in vitro(p<0.05). In vivo experiments using PC-3 human prostate cancer animal model demonstrated that tumor volume and growth at the conclusion of experiment was significantly attenuated in the suicide toxic gene therapy (Ad-CMV-TK / ACV) group compared with Ad-CMV-TK, ACV and no treatment control groups(p<0.05).CONCLUSIONS:
Adenovirus-mediated suicide gene therapy using HSV-TK / ACV system provides an effective therapy in an experimental human prostate cancer animal model by significantly inhibiting tumor growth.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fosforilação
/
Fosfotransferases
/
Próstata
/
Neoplasias da Próstata
/
Suicídio
/
Timidina Quinase
/
Aciclovir
/
Terapia Genética
/
Adenoviridae
/
Beta-Galactosidase
Limite:
Animais
/
Humanos
Idioma:
Coreano
Revista:
Korean Journal of Urology
Ano de publicação:
1999
Tipo de documento:
Artigo
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