RECOMBINANT ADENOVIRUS VECTOR EXPRESSING WILD-TYPE P53 IS A POTENT INHIBITOR OF PROSTATE-CANCER CELL-PROLIFERATION

Objectives. A recombinant adenovirus vector (AdWTp53) expressing wild- type p53 was evaluated for its cell growth inhibitory effects on metas tatic human prostate cancer cells. Methods. Human prostate cancer cell s LNCaP, DU145, PC3, 1LN, and DUPro-1 were infected with AdWTp53 vecto r and expression of exogenous p53 in these cells was analyzed by immun oprecipitation and western blot assays. The cell growth inhibitory eff ects of AdWTp53 were determined by counting cell number on a hemocytom eter or by crystal violet staining of cells after infection with AdWTp 53. The p53-regulated gene WAF1 and DNA fragmentation were also analyz ed in prostate cancer cells infected with AdWTp53. Results. High level s of the AdWTp53 vector-derived p53 protein were present in metastatic prostate cancer cells, and the p53-regulated gene WAF1 was induced in these cells. Infection of these tumor cell lines with AdWTp53 vector resulted in severe growth inhibition and cell death in comparison to u ntreated or control adenovirus vector-infected cells. Furthermore, fra gmentation of genomic DNA, a property associated with apoptosis, was a lso observed in prostate cancer cells infected with AdWTp53. Conclusio ns. AdWTp53 vector exhibited a potent inhibitory effect on the growth of all of human metastatic prostate cancer cells, and both cytostatic and cytotoxic effects of AdWTp53 were observed. The induction of p53-r egulated gene WAF1 in AdWTp53-infected prostate cancer cells suggests the involvement of cellular p53 pathway in the cell growth inhibition. These results provide a molecular basis for further evaluation of ant itumorigenic effects of AdWTp53 vector in animal models of prostate ca ncer.