Nitric Oxide Gene Therapy for Prostate Cancer
Final rept. 1 Oct 1998-30 Mar 2001
WILLIAM BEAUMONT HOSPITAL ROYAL OAK MI
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Traditional therapies for advanced prostate cancer are unable to cure a majority of patients. An approach to therapy we have tested involves production of nitric oxide NO by introduction of replication defective adenovirus containing the DNA sequences for inducible nitric oxide synthase iNOS. An adenovirus vector with an iNOS cDNA and a CMV promoter Ad5-CMV-iNOS was constructed and tested. The production of nitric oxide in prostate cancer cells after infection with Ad5-CMV-iNOS was measured. Maximum NO release rate occurred when cells were infected at multiplicity of infection MOl 15 and after 24 to 36 hours incubation. Direct cell killing of cells growing in monolayer commenced within 1 day after infection and occurred at MOl greater than 5. An in vitro cell survival investigation utilized Du-145 and PC-3 prostate tumor cells growing to high density in a collagen matrix. Both control viral vector and Ad5-CMV-iNOS produced direct cell kill but no radiation sensitization in these cell systems. Sensitization was not observed in either aerobic or hypoxic conditions. Sensitization was also not observed after Ad5-CMV-iNOS gene therapy of Du-145 and PC-3 xenograft tumors in nude mice as assayed by the in vivoin vitro method.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research