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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 volume 10, pages 898–906 (2003)Cite this article

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.

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Acknowledgements

This work was supported by the Leukämie Liga Duesseldorf.

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Authors and Affiliations

  1. Klinik für Hämatologie, Onkologie und klinische Immunologie, Heinrich-Heine-Universität Düsseldorf, Moorenstraße 5, Düsseldorf, D-40225, Germany

    Ulrich-Peter Rohr, Marc-Andre Wulf, Susanne Stahn, Florian Heyd, Ulrich Steidl, Roland Fenk, Rainer Haas & Ralf Kronenwett

  2. Innere Klinik und Poliklinik (Tumorforschung), Universitätsklinikum Essen, Hufelandstraße 55, D-45122, Germany

    Bertram Opalka

  3. Institut für Onkologische Chemie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

    Gerald Pitschke, Hans-Bernd Prisack & Hans Bojar

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  1. Ulrich-Peter Rohr
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Correspondence to Ulrich-Peter Rohr.

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Rohr, UP., Wulf, MA., Stahn, S. et al. Non-small lung cancer cells are prime targets for p53 gene transfer mediated by a recombinant adeno-associated virus type-2 vector. Cancer Gene Ther 10, 898–906 (2003). https://doi.org/10.1038/sj.cgt.7700643

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  • DOI: https://doi.org/10.1038/sj.cgt.7700643

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