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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2007-01-19

AUTHORS

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

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. More... »

PAGES

431-439

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.cgt.7701029

DOI

http://dx.doi.org/10.1038/sj.cgt.7701029

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1011029610

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17235352


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59 clinical trials
60 clonogenic growth
61 colonies
62 colony formation
63 combination
64 combination of bortezomib
65 comparison
66 compounds
67 concentration
68 contrast
69 cytotoxic effects
70 docetaxel
71 drug concentrations
72 effect
73 formation
74 gene transfer
75 growth
76 increase
77 inhibition
78 inhibitor bortezomib
79 intracellular p53 levels
80 levels
81 lines
82 low cytotoxic effect
83 lung cancer cell lines
84 non-small cell lung cancer cell lines
85 observed antagonistic effects
86 p53
87 p53 gene transfer
88 p53 levels
89 p53 restoration
90 p53 status
91 proteasome inhibitor bortezomib
92 rAAV
93 rate
94 reduced ability
95 reduction
96 report
97 restoration
98 significant reduced ability
99 significant synergistic inhibition
100 single agent
101 status
102 synergistic inhibition
103 toxicity
104 transfer
105 treatment
106 trials
107 tumor cell growth
108 tumor cell toxicity
109 type 2
110 virus type 2
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