p53 Adenoviral vector (Ad-CMV-p53) induced prostatic growth inhibition of primary cultures of human prostate and an experimental rat model

Citation
T. Shirakawa et al., p53 Adenoviral vector (Ad-CMV-p53) induced prostatic growth inhibition of primary cultures of human prostate and an experimental rat model, J GENE MED, 2(6), 2000, pp. 426-432
Citations number
22
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
JOURNAL OF GENE MEDICINE
ISSN journal
1099-498X → ACNP
Volume
2
Issue
6
Year of publication
2000
Pages
426 - 432
Database
ISI
SICI code
1099-498X(200011/12)2:6<426:PAV(IP>2.0.ZU;2-1
Abstract
Background Benign prostatic hyperplasia (BPH) is the most common proliferat ive disease affecting men. Numerous minimally invasive technologies are bei ng developed or are currently in use to obviate the need for transurethral surgery. The goal of the present study was to develop a novel molecular bas ed approach for the treatment of BPH using recombinant p53 adenoviral vecto r. The over-expression of wt-p53 can cause cell apoptosis or cell growth ar rest, thus preventing the uncontrolled cell proliferation underlying BPH pa thophysiology. Methods Ad-CMV-p53, a replication-deficient recombinant adenovirus containi ng cytomegalovirus promoter driving p53 gene, was used. Human prostate stro mal CPS) cells were evaluated for apoptosis (TUNEL assay), mRNA levels of k ey cell cycle regulators influencing apoptosis (p-53, Bax and Bcl-2) using quantitative RT-PCR and cytotoxicity after Ad-CMV-p53. Ad-CMV-p53 was unila terally injected into rat ventral prostates and growth inhibition was measu red by prostate weight 3 weeks after injection. Results In vitro exposure to Ad-CMV-p53 significantly inhibited the prolife ration of PS cells, induced mRNA over-expression of both wt-p53 and Bax, an d increased the proportion of apoptotic cells. A 30% decrease in average pr ostate weight was demonstrated in rodents after Ad-CMV-p53 injection. Conclusions The results suggest that further investigation of molecular gen e therapy with recombinant wt-p53 adenovirus for the treatment of BPH is wa rranted. Copyright (C) 2000 John Wiley & Sons, Ltd.