title: Non-small lung cancer cells are prime targets for p53 gene transfer mediated by a recombinant adeno-associated virus type-2 vector.
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.
authors.affiliation: Klinik für Hämatologie, Onkologie und klinische Immunologie, Heinrich-Heine-Universität Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany. urohr-uni-duesseldorf@gmx.de
authors.forename: Ulrich-Peter
authors.initials: UP
authors.lastname: Rohr
authors.forename: Marc-Andre
authors.initials: MA
authors.lastname: Wulf
authors.forename: Susanne
authors.initials: S
authors.lastname: Stahn
authors.forename: Florian
authors.initials: F
authors.lastname: Heyd
authors.forename: Ulrich
authors.initials: U
authors.lastname: Steidl
authors.forename: Roland
authors.initials: R
authors.lastname: Fenk
authors.forename: Bertram
authors.initials: B
authors.lastname: Opalka
authors.forename: Gerald
authors.initials: G
authors.lastname: Pitschke
authors.forename: Hans-Bernd
authors.initials: HB
authors.lastname: Prisack
authors.forename: Hans
authors.initials: H
authors.lastname: Bojar
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.forename: Ralf
authors.initials: R
authors.lastname: Kronenwett
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002455:Cell Division; D045744:Cell Line, Tumor; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology; D018014:Gene Transfer Techniques; D016158:Genes, p53; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D014161:Transduction, Genetic; D018523:Tropism
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin