The growth inhibitory effect of p21 adenovirus on androgen-dependent and -independent human prostate cancer cells.
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.


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.
Gotoh
A
A
International Centre for Medical Research and Department of Urology, Kobe University School of Medicine, Kobe, Japan. gotoh@med.kobe-u.ac.jp
Shirakawa
T
T
Wada
Y
Y
Fujisawa
M
M
Okada
H
H
Kamidono
S
S
Hamada
K
K
D000256:Adenoviridae; D000728:Androgens; D002455:Cell Division; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000008:administration & dosage / Q000235:genetics*; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D014407:Tumor Cells, Cultured
D000728:Androgens; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins