Inhibition of growth of human prostate cancer xenograft by transfection of p53 gene: gene transfer by electroporation.
To date, there is no effective therapy for hormone-independent prostate cancer. Therefore, as a new strategy for refractory cancer, gene therapy is showing increasing promise. In this study, we attempted to use a nonviral gene transfer system, in vivo electroporation, in prostate cancer cell PC-3 xenografts with the wild-type p53 (wt-p53) gene, as gene therapy for hormone-independent prostate cancer. To evaluate this in vivo gene transfer method, the beta-galactosidase gene was transfected into xenografts by electroporation. Then, the efficiency of transfection of exogenous p53 gene by electroporation was confirmed by reverse transcription-PCR, which indicated that p53 mRNA was present in samples from xenografts. Next, to estimate the reduction of prostate cancer xenografts by this method, we measured the size of PC-3 xenografts in nude mice after electroporation with the wt-p53 gene. The growth of tumors was markedly suppressed by wt-p53 gene transfection by electroporation compared with transfection of mutated type p53 gene (P = 0.0027) or vector only (P = 0.0015). Furthermore, histological specimens revealed increased apoptotic cell death in p53-transfected tumors. These results suggest that it is possible to transfer wt-p53 into prostate cancer xenografts using electroporation and to suppress the growth of tumors; they, furthermore, suggest that this system might be used for local advanced hormone-independent prostate cancer.
Mikata
Kunihisa
K
Department of Urology, Department of Pathology, Yokohama City University School of Medicine, Yokohama, 236-0004, Japan.
Uemura
Hiroji
H
Ohuchi
Hideki
H
Ohta
Shinsuke
S
Nagashima
Yoji
Y
Kubota
Yoshinobu
Y
D000818:Animals; D017209:Apoptosis; D017931:DNA Primers / Q000737:chemistry; D018274:Electroporation / Q000379:methods*; D016158:Genes, p53 / Q000235:genetics*; D015316:Genetic Therapy; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017354:Point Mutation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D012333:RNA, Messenger; D001616:beta-Galactosidase