Delivery of the p53 tumor suppressor gene into lung cancer cells by an adenovirus/DNA complex

Dao M. Nguyen, Sandra A. Wiehle, Patricia E. Koch, Cynthia Branch, Nancy Yen, Jack A. Roth, Richard J. Cristiano

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

An adenovirus/DNA complex was constructed by chemically linking poly-L-lysine to the capsid of the replication-defective adenovirus dl312, allowing for coupling with plasmid DNA by an ionic interaction. We have previously demonstrated that this adenovirus/DNA complex can efficiently transduce malignant cells with a plasmid expressing the β-galactosidase gene both in vitro and in vivo. In this report, we show that this system can deliver a therapeutic gene that encodes for the tumor suppressor protein p53 to lung cancer cells, both in vitro and in vivo, leading to significant biological effects. Transfection of the p53-negative human lung cancer cell line H1299 with the adenovirus/DNA complex carrying a plasmid expressing the p53 gene resulted in high levels of p53 protein and induction of apoptosis. Injection of the complex carrying the p53 gene to subcutaneous tumor sites 5 days after tumor cell implantation resulted in a significant inhibition of tumorigenicity as measured by the number and size of tumors that developed 21 days after treatment. Three and six injections of the complex carrying the p53 gene into H1299 subcutaneous tumor nodules led to significant dose-related tumor growth suppression 18 days after the first injection compared with control-treated tumors. This adenovirus/DNA complex, therefore, is capable of efficiently delivering the p53 gene into malignant cells in vitro and in vivo and now provides a general gene delivery vector that is simple to construct and capable of testing therapeutic genes in malignant cells.

Original languageEnglish (US)
Pages (from-to)191-198
Number of pages8
JournalCancer gene therapy
Volume4
Issue number3
StatePublished - 1997

Keywords

  • Adenovirus/PLL/DNA complex
  • p53 tumor suppressor gene

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

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  • Cite this

    Nguyen, D. M., Wiehle, S. A., Koch, P. E., Branch, C., Yen, N., Roth, J. A., & Cristiano, R. J. (1997). Delivery of the p53 tumor suppressor gene into lung cancer cells by an adenovirus/DNA complex. Cancer gene therapy, 4(3), 191-198.