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 G. Steidl, Roland Fenk, Bertram Opalka, Gerald Pitschke, Hans Bernd Prisack, Hans Bojar, Rainer Haas, Ralf Kronenwett

Research output: Contribution to journalArticle

8 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Dependovirus
p53 Genes
Non-Small Cell Lung Carcinoma
Cisplatin
Growth
Neoplasm Genes
Cell Line
Genetic Therapy
Neoplasms
Tropism
Small Cell Carcinoma
Virus Diseases
Lung Neoplasms
Complementary DNA
Apoptosis

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Non-small lung cancer cells are prime targets for p53 gene transfer mediated by a recombinant adeno-associated virus type-2 vector. / Rohr, Ulrich Peter; Wulf, Marc Andre; Stahn, Susanne; Heyd, Florian; Steidl, Ulrich G.; Fenk, Roland; Opalka, Bertram; Pitschke, Gerald; Prisack, Hans Bernd; Bojar, Hans; Haas, Rainer; Kronenwett, Ralf.

In: Cancer Gene Therapy, Vol. 10, No. 12, 12.2003, p. 898-906.

Research output: Contribution to journalArticle

Rohr, UP, Wulf, MA, Stahn, S, Heyd, F, Steidl, UG, Fenk, R, Opalka, B, Pitschke, G, Prisack, HB, 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, vol. 10, no. 12, pp. 898-906. https://doi.org/10.1038/sj.cgt.7700643
Rohr, Ulrich Peter ; Wulf, Marc Andre ; Stahn, Susanne ; Heyd, Florian ; Steidl, Ulrich G. ; Fenk, Roland ; Opalka, Bertram ; Pitschke, Gerald ; Prisack, Hans Bernd ; Bojar, Hans ; Haas, Rainer ; Kronenwett, Ralf. / Non-small lung cancer cells are prime targets for p53 gene transfer mediated by a recombinant adeno-associated virus type-2 vector. In: Cancer Gene Therapy. 2003 ; Vol. 10, No. 12. pp. 898-906.
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