Inhibition of the growth of pre-established subcutaneous tumor nodules of human prostate cancer cells by single injection of the recombinant adenovirus p53 expression vector.
We have previously described potent growth-inhibitory effect of a recombinant adenovirus expressing wild type p53 (AdWTp53) in metastatic prostate cancer cells via activation of cellular p53 pathways. We have extended these observations to analyze the effects of AdWTp53 on primary cultures of radical prostatectomy specimens (RPS) and have also evaluated the gene therapeutic potential of the AdWTp53 in a nude mice model. Infection of primary cultures of prostate cancer specimens resulted in about 80% cell growth inhibition in comparison with cultures treated with control adenovirus dl312. Single injection of AdWTp53 into pre-established tumor nodules of DU145 prostate cancer cells suppressed tumor growth significantly (p = 0.0407) as determined by comparison of tumor volumes of the AdWTp53-treated vs. control vector (dl312) or PBS-treated groups. Moreover, there was no significant difference in tumor growth inhibition between single vs. multiple injections of AdWTp53. Our observations support the potential of AdWTp53 for gene therapy of prostate cancer.
Asgari
K
K
Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA.
Sesterhenn
I A
IA
McLeod
D G
DG
Cowan
K
K
Moul
J W
JW
Seth
P
P
Srivastava
S
S
D000256:Adenoviridae; D000818:Animals; D002455:Cell Division; D016158:Genes, p53; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009367:Neoplasm Staging; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000601:surgery / Q000628:therapy*; D011994:Recombinant Proteins / Q000096:biosynthesis; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53