1. Inhibition of growth of human prostate cancer xenograft by transfection of p53 gene: gene transfer by electroporation.
- Author
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Mikata K, Uemura H, Ohuchi H, Ohta S, Nagashima Y, and Kubota Y
- Subjects
- Animals, Apoptosis, DNA Primers chemistry, Humans, In Situ Nick-End Labeling, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Point Mutation, Prostatic Neoplasms pathology, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Transplantation, Heterologous, Tumor Cells, Cultured, beta-Galactosidase genetics, beta-Galactosidase metabolism, Electroporation methods, Genes, p53 genetics, Genetic Therapy, Prostatic Neoplasms genetics, Prostatic Neoplasms therapy, Transfection
- Abstract
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.
- Published
- 2002