OBJECTIVE: To assess the potential of p21 as a gene therapy treatment for prostate cancer, by introducing p21 into both androgen-dependent (AD) and -independent (AI) human prostate cancer cell lines via a recombinant adenoviral vector, Ad5CMV-p21, carrying human p21 cDNA. MATERIALS AND METHODS: The LNCaP, DU145 and PC-3 human prostate cancer cell lines were cultured and infected with Ad5CMV-p21. Cell growth, cell-cycle progression and tumorigenicity were then assessed by thymidine incorporation into cellular DNA, and cell number, flow cytometry, and tumour growth after inoculating the cells into nude mice. RESULTS: Growth was inhibited in Ad5CMV-p21 viral-infected AD and AI prostate cancer cells. The effects were dose-dependent, regardless of the androgen status of the cell lines. Flow cytometric analysis showed that Ad5CMV-p21 arrested cell-cycle progression at G1/S with no appreciable effect on the levels of apoptotic cells. The tumorigenicity of cancer cells infected with Ad5CMV-p21 was greatly reduced in athymic mice. CONCLUSIONS: These results suggest that Ad5CMV-p21 may be a new therapeutic agent for human prostate cancer gene therapy.
OBJECTIVE: To assess the potential of p21 as a gene therapy treatment for prostate cancer, by introducing p21 into both androgen-dependent (AD) and -independent (AI) humanprostate cancer cell lines via a recombinant adenoviral vector, Ad5CMV-p21, carrying humanp21 cDNA. MATERIALS AND METHODS: The LNCaP, DU145 and PC-3 humanprostate cancer cell lines were cultured and infected with Ad5CMV-p21. Cell growth, cell-cycle progression and tumorigenicity were then assessed by thymidine incorporation into cellular DNA, and cell number, flow cytometry, and tumour growth after inoculating the cells into nude mice. RESULTS: Growth was inhibited in Ad5CMV-p21viral-infected AD and AI prostate cancer cells. The effects were dose-dependent, regardless of the androgen status of the cell lines. Flow cytometric analysis showed that Ad5CMV-p21 arrested cell-cycle progression at G1/S with no appreciable effect on the levels of apoptotic cells. The tumorigenicity of cancer cells infected with Ad5CMV-p21 was greatly reduced in athymic mice. CONCLUSIONS: These results suggest that Ad5CMV-p21 may be a new therapeutic agent for humanprostate cancer gene therapy.
Authors: Stefan Ambs; Robyn L Prueitt; Ming Yi; Robert S Hudson; Tiffany M Howe; Fabio Petrocca; Tiffany A Wallace; Chang-Gong Liu; Stefano Volinia; George A Calin; Harris G Yfantis; Robert M Stephens; Carlo M Croce Journal: Cancer Res Date: 2008-08-01 Impact factor: 12.701