Adenovirus-mediated suicide-gene therapy using the herpes simplex virus thymidine kinase gene in cell and animal models of human prostate cancer: changes in tumour cell proliferative activity.

摘要: Objectives To determine the feasibility and efficacy of suicide-gene therapy using adenovirus (Ad)-mediated herpes simplex virus thymidine kinase (HSV-TK) prodrug acyclovir, to evaluate changes in biological phenotype for tumour cell proliferative activity after animal models human prostate cancer. Materials methods Using a replication-defective adenoviral vector (cytomegalovirus, CMV) containing β-galactosidase gene (Ad-CMV-β-gal) as control Ad-CMV-TK therapeutic under transcriptional CMV promoter, transduction efficiency was assessed vitro by infecting LNCaP PC-3 androgen-dependent independent cancer cells with Ad-CMV-β-gal, X-gal staining. The TK infected determined measuring TK-mediated [3H]-gancyclovir phosphorylation. sensitivity infection or without acyclovir. inhibition growth vivo induced Ad-CMV-TK/acyclovir system separate controlled experiments mouse models. Ki-67 antigen proliferating nuclear (PCNA), both useful indices, were evaluated immunohistochemical staining (MIB-1 monoclonal antibody anti-PCNA antibody) formalin-fixed, paraffin-embedded tissues from therapy-treated animals. Results mean significantly higher than used (P < 0.05). inhibited adding acyclovir In model, volume lower mice treated those only, only untreated (controls) Histochemical showed that destroyed tumours through death apoptosis, local lymphatic infiltration. PCNA labelling index controls (P < 0.05, Mann–Whitney U-test). also Student’s t-test). Adenovirus-mediated HSV-TK decreased prostatic vivo. Conclusions an HSV-TK/acyclovir provided effective experimental inhibiting decreasing cells. Such could be developed novel method treating patients androgen-independent cancer.