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 journalArticle

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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
Pages (from-to)1665-1671
Number of pages7
JournalClinical Cancer Research
Volume2
Issue number10
StatePublished - Oct 1 1996
Externally publishedYes

Fingerprint

p53 Genes
Ionizing Radiation
Colorectal Neoplasms
Gene Expression
Radiation Tolerance
Biotin
Genetic Therapy
Neoplasms
DNA Nucleotidylexotransferase
Transferases
Heterografts
Adenoviridae
Animal Models
Apoptosis
Staining and Labeling
Cell Line
Mutation
Growth
Infection

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Spitz, F. R., Nguyen, D., Skibber, J. M., Meyn, R. E., Cristiano, R. J., & Roth, J. A. (1996). Adenoviral-mediated wild-type p53 gene expression sensitizes colorectal cancer cells to ionizing radiation. Clinical Cancer Research, 2(10), 1665-1671.

Adenoviral-mediated wild-type p53 gene expression sensitizes colorectal cancer cells to ionizing radiation. / Spitz, Francis R.; Nguyen, Dao; Skibber, John M.; Meyn, Raymond E.; Cristiano, Richard J.; Roth, Jack A.

In: Clinical Cancer Research, Vol. 2, No. 10, 01.10.1996, p. 1665-1671.

Research output: Contribution to journalArticle

Spitz, FR, Nguyen, D, Skibber, JM, Meyn, RE, Cristiano, RJ & Roth, JA 1996, 'Adenoviral-mediated wild-type p53 gene expression sensitizes colorectal cancer cells to ionizing radiation', Clinical Cancer Research, vol. 2, no. 10, pp. 1665-1671.
Spitz, Francis R. ; Nguyen, Dao ; Skibber, John M. ; Meyn, Raymond E. ; Cristiano, Richard J. ; Roth, Jack A. / Adenoviral-mediated wild-type p53 gene expression sensitizes colorectal cancer cells to ionizing radiation. In: Clinical Cancer Research. 1996 ; Vol. 2, No. 10. pp. 1665-1671.
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