Gene Therapy for Prostate Cancer Radiosensitization Using Mutant Poly (ADP-Ribose) Polymerase
Abstract
During the first three years of funding the authors developed recombinant plasmids expressing the DNA-binding domain of poly(ADP-ribose) polymerase (PARP-DBD) under the control of the 5'-flanking sequences of the human prostate-specific antigen (PSA) gene, and demonstrated that PARP-DBD sensitized prostate cancer cells to DNA-damaging agents in vitro. The present study is designed to assess the efficiency of this strategy in vivo. Towards this end, they developed a cationic liposome-mediated gene delivery of the PARP-DBD expressing plasmid in tumor xenografts of PSA-producing and androgen-sensitive prostate cancer cells (22Rv1 cell line). Tumor-bearing mice were treated intratumorally with liposome-complexed plasmid for PARP-DBD (LE-PARP-DBD), ionizing radiation (IR), or a combination of LE-PARP-DBD and IR. The results showed that administration of LE-PARP-DBD resulted in the expression of dominant-negative mutant of PARP in 22Rv1 tumor xenografts and enhanced radiation-induced inhibition of tumor growth in vivo. These data indicate that expression of the PARP-DBD in PSA-producing prostate cancer cells show potential to radiosensitize prostate tumor cells in vivo. (5 figures, 4 refs.)
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA418061
Entities
People
- Viatcheslav Soldatenkov
Organizations
- Georgetown University