Adenoviral-mediated wild-type p53 gene expression sensitizes colorectal cancer cells to ionizing radiation

Francis R. Spitz, Dao Nguyen, John M. Skibber, Raymond E. Meyn, Richard J. Cristiano, Jack A. Roth

Research output: Contribution to journalArticlepeer-review

183 Scopus citations

Abstract

Wild-type p53 gene transfer into the SW620 colorectal carcinoma cell line was performed using the replication-defective adenovirus Ad5/CMV/p53 to evaluate the effect of wild-type p53 expression on radiation sensitivity. The results indicated that infection with Ad5/CMV/p53 sensitized the cells. The survival at 2 Gy was reduced from 55 to 23%. Flow cytometric analysis of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay-labeled cells and in situ TUNEL staining of xenograft tumors demonstrated an increase in labeled cells with combination treatment, indicating increased apoptosis in cells treated with Ad5/CMV/p53 before irradiation. A significant enhancement of tumor growth suppression by this combination strategy was observed in a s.c. tumor animal model compared to p53 gene therapy alone. The delay in regrowth to control tumor size of 1000 mm3 was 2 days for 5 Gy, 15 days for Ad5/CMV/p53, and 37 days for Ad5/CMV/p53 + 5 Gy, indicating synergistic interactions. These data indicate that the delivery of wild-type p53 to cells with p53 mutations increases their radiation sensitivity, and this may be accomplished by adenoviral-mediated gene therapy.

Original languageEnglish (US)
Pages (from-to)1665-1671
Number of pages7
JournalClinical Cancer Research
Volume2
Issue number10
StatePublished - Oct 1996
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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