Non-small lung cancer cells are prime targets for p53 gene transfer mediated by a recombinant adeno-associated virus type-2 vector

Ulrich Peter Rohr, Marc Andre Wulf, Susanne Stahn, Florian Heyd, Ulrich Steidl, Roland Fenk, Bertram Opalka, Gerald Pitschke, Hans Bernd Prisack, Hans Bojar, Rainer Haas, Ralf Kronenwett

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

In this study, we elucidated the potential of recombinant adeno-associated virus type-2 (rAAV-2) vectors for lung cancer gene therapy. Cell lines of the three major histological subtypes of non-small cell lung cancer (NSCLC) were highly susceptible for rAAV-2 showing transduction rates between 63.4 and 98.9%. In contrast, cell lines of small cell carcinomas were resistant to rAAV-2 infection. For restoration of p53 function in p53 deficient NSCLC, a rAAV-2 vector was constructed containing wt p53 cDNA. Following transduction with rAAV-p53, cell growth of all NSCLC cell lines was significantly reduced in a dose-dependent manner between 44 and 71.7% in comparison with rAAV-GFP transduced cells. The reduction of tumor cell growth was associated with increased apoptosis. Adding cisplatin to rAAV-p53-infected cells led to a significant growth inhibition between 81 and 91% indicating a synergistic effect between cisplatin and rAAV-p53. Interestingly, the tumor cells surviving cisplatin and rAAV-p53 treatment were inhibited in their ability to form colonies as reflected by a reduction of colony growth between 57 and 90.4%. In conclusion, rAAV-2 vectors exhibit a strong tropism for NSCLC. Successful inhibition of tumor cell growth following transduction with a rAAV-p53 vector underlines the potential role of rAAV-2 in cancer gene therapy.

Original languageEnglish (US)
Pages (from-to)898-906
Number of pages9
JournalCancer gene therapy
Volume10
Issue number12
DOIs
StatePublished - Dec 2003

Keywords

  • AAV-2
  • Apoptosis
  • Lung cancer
  • P53
  • Tropism

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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  • Cite this

    Rohr, U. P., Wulf, M. A., Stahn, S., Heyd, F., Steidl, U., Fenk, R., Opalka, B., Pitschke, G., Prisack, H. B., Bojar, H., Haas, R., & Kronenwett, R. (2003). Non-small lung cancer cells are prime targets for p53 gene transfer mediated by a recombinant adeno-associated virus type-2 vector. Cancer gene therapy, 10(12), 898-906. https://doi.org/10.1038/sj.cgt.7700643