The proteasome inhibitor bortezomib acts differently in combination with p53 gene transfer or cytotoxic chemotherapy on NSCLC cells

J. Neukirchen, A. Meier, A. Rohrbeck, G. Garcia-Pardillos, Ulrich G. Steidl, R. Fenk, R. Haas, R. Kronenwett, U. P. Rohr

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

In this report, the effects of a combined treatment with the proteasome inhibitor bortezomib and either a recombinant adeno-associated virus type 2 (rAAV-2)-mediated p53 gene transfer or chemotherapeutic agents, docetaxel and pemetrexed, were tested on p53 positive and p53negative non-small cell lung cancer (NSCLC) cell lines. The combination of bortezomib and rAAV-p53 led to a significant synergistic inhibition of cell growth between 62-82% depending on the p53 status of the cell line and drug concentration. Surviving cells of the combined treatment showed a significant reduced ability to form colonies. Enhanced cell toxicity was associated with a 5.3-14.4-fold increase of the apoptotic rate and intracellular p53 level up to 50.4% following vector-mediated p53 restoration and bortezomib treatment. In contrast, an antagonistic effect on tumor cell growth and colony formation was observed for the combination of bortezomib and docetaxel or pemetrexed as a reduction of cell growth between 31 and 48% was found in comparison to 50% using the single agents. Lower cytotoxic effects were associated with significantly reduced apoptosis and an increase of clonogenic growth. The observed antagonistic effects between bortezomib and docetaxel or pemetrexed might influence clinical trials using these compounds. Conversely, p53 restoration and bortezomib treatment led to enhanced, synergistic tumor cell toxicity.

Original languageEnglish (US)
Pages (from-to)431-439
Number of pages9
JournalCancer Gene Therapy
Volume14
Issue number4
DOIs
StatePublished - Apr 2007
Externally publishedYes

Fingerprint

Proteasome Inhibitors
p53 Genes
docetaxel
Non-Small Cell Lung Carcinoma
Pemetrexed
Drug Therapy
Growth
Cell Line
Dependovirus
Therapeutics
Bortezomib
Neoplasms
Clinical Trials
Apoptosis
Pharmaceutical Preparations

Keywords

  • Bortezomib
  • Docetaxel
  • Pemetrexed
  • rRAAV-p53

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

The proteasome inhibitor bortezomib acts differently in combination with p53 gene transfer or cytotoxic chemotherapy on NSCLC cells. / Neukirchen, J.; Meier, A.; Rohrbeck, A.; Garcia-Pardillos, G.; Steidl, Ulrich G.; Fenk, R.; Haas, R.; Kronenwett, R.; Rohr, U. P.

In: Cancer Gene Therapy, Vol. 14, No. 4, 04.2007, p. 431-439.

Research output: Contribution to journalArticle

Neukirchen, J, Meier, A, Rohrbeck, A, Garcia-Pardillos, G, Steidl, UG, Fenk, R, Haas, R, Kronenwett, R & Rohr, UP 2007, 'The proteasome inhibitor bortezomib acts differently in combination with p53 gene transfer or cytotoxic chemotherapy on NSCLC cells', Cancer Gene Therapy, vol. 14, no. 4, pp. 431-439. https://doi.org/10.1038/sj.cgt.7701029
Neukirchen, J. ; Meier, A. ; Rohrbeck, A. ; Garcia-Pardillos, G. ; Steidl, Ulrich G. ; Fenk, R. ; Haas, R. ; Kronenwett, R. ; Rohr, U. P. / The proteasome inhibitor bortezomib acts differently in combination with p53 gene transfer or cytotoxic chemotherapy on NSCLC cells. In: Cancer Gene Therapy. 2007 ; Vol. 14, No. 4. pp. 431-439.
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