In vivo adenovirus-mediated p53 tumor suppressor gene therapy for colorectal cancer

Francis R. Spitz, Dao Nguyen, John M. Skibber, James Cusack, Jack A. Roth, Richard J. Cristiano

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

Background: The p53 tumor suppressor gene is altered in up to 70% of colorectal cancers. Materials and Methods: We infected the colorectal cancer cell lines SW620 and KM12L4, in which p53 is mutated, with the replication-defective adenovirus Ad5/CMV/p53 to evaluate the effects of adenovirus-mediated wild-type p53 gene transfer Gene transduction was measured by cytochemical staining of cells infected with the Ad5/CMV/β-gal virus and expression of the wildtype p53 protein in these cells was demonstrated by immunoblotting. Results: Significant suppression of in vitro cell proliferation and induction of apoptosis (as measured by TUNEL assay labeling) were observed following Ad5/CMV/p53 infection. More importantly, similar effects were observed in vivo in an established nude mouse subcutaneous tumor model; significant suppression of tumor growth (60% 70%) and induction of apoptosis were observed following intratumoral injections of Ad5/CMV/p53. Conclusion: This form of therapy may provide a novel approach to colorectal cancer.

Original languageEnglish (US)
Pages (from-to)3415-3422
Number of pages8
JournalAnticancer research
Volume16
Issue number6 B
StatePublished - Dec 1 1996
Externally publishedYes

Keywords

  • Adenovirus
  • Colon cancer
  • Gene therapy
  • p53

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Spitz, F. R., Nguyen, D., Skibber, J. M., Cusack, J., Roth, J. A., & Cristiano, R. J. (1996). In vivo adenovirus-mediated p53 tumor suppressor gene therapy for colorectal cancer. Anticancer research, 16(6 B), 3415-3422.