Gene therapy for primary and metastatic pancreatic cancer with intraperitoneal retroviral vector bearing the wild-type p53 gene

R. F. Hwang, E. Maria Gordon, W. French Anderson, D. Parekh, K. D. Lillemoe, J. C. Thompson, Jr Townsend, S. M. Vickers, R. Daniel Beauchamp, J. G. Norman

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58 Scopus citations

Abstract

Background. Metastatic pancreatic cancer is uniformly fatal because no effective chemotherapy is available. Mutations in the p53 tumor suppressor gene are found in up to 70% of pancreatic adenocarcinomas. We examined the efficacy of a retroviral vector containing the wild-type p53 gene on metastatic pancreatic cancer in a nude mouse model. Methods. Bxpc3 human pancreatic cancer cells were transduced with either a retroviral p53 vector or an LXSN emtpy vector. Cells were examined for incorporation of triatiated thymidine to determine the effect of p53 retroviral transduction on DNA synthesis, and a TACS2 assay for apoptosis was performed. The functional activity of p53 in transduced cells was assayed by Western blot analysis with an antibody to WAF1/p21. In vivo effects of intraperitoneal injections of the p53 vector was examined in a nude mouse model of peritoneal carcinomatosis. Results. Cells treated with the p53 vector exhibited a 59% to 85.5% reduction in cell number comapred with the control cells (P < .05). p53-treated cells demonstrated decreased incorporation of tritiated thymidine (12.7% ± 0.7% vs 17.5% ± 1.4%; P = .002), increased staining for apoptosis, and increased expression of the WAF1/p21 protein. Treatment of nude mice with the retroviral p53 vector resulted in a significant inhibition of growth of the primary pancreatic tumor, as well as the peritoneal tumor deposits, compared with the LXSN control vector. Conclusions. Intraperitoneal delivery of a retroviral p53 vector may provide a nude treatment approach for peritoneal carcinomatosis from pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)143-151
Number of pages9
JournalSurgery
Volume124
Issue number2
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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