Source:http://linkedlifedata.com/resource/pubmed/id/16988940
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
2006-10-26
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pubmed:abstractText |
The potential of the novel insulin-like growth factor receptor (IGF-IR) inhibitor NVP-AEW541 as an antiproliferative agent in human neuroblastoma was investigated. Proliferation of a panel of neuroblastoma cell lines was inhibited by NVP-AEW541 with IC(50) values ranging from 0.15 to 5 microM. Experiments using an IGF-IR neutralizing antibody confirmed that the IGF-IR was essential to support growth of neuroblastoma cell lines. The expression levels of the IGF-IR in individual neuroblastoma cell lines did not correlate with the sensitivities to NVP-AEW541, while coexpression of the IGF-IR and the insulin receptor (IR) correlated with lower sensitivity to the inhibitor in some cell lines. Intriguingly, high levels of activation of Akt/protein kinase B (PKB) and phosphorylation of the ribosomal S6 protein were observed in neuroblastoma cell lines with decreased sensitivities to NVP-AEW541. Inhibition of Akt/PKB activity restored the sensitivity of neuroblastoma cells to the IGF-IR inhibitor. Transfection of neuroblastoma cells with activated Akt or ribosomal protein S6 kinase (S6K) decreased the sensitivity of the cells to NVP-AEW541. IGF-I-stimulated proliferation of neuroblastoma cell lines was completely blocked by NVP-AEW541, or by a combination of an inhibitor of phosphoinositide 3-kinase and rapamycin. In addition to its antiproliferative effects, NVP-AEW541 sensitized neuroblastoma cells to cisplatin-induced apoptosis. Together, our data demonstrate that NVP-AEW541 in combination with Akt/PKB inhibitors or chemotherapeutic agents may represent a novel approach to target human neuroblastoma cell proliferation.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0020-7136
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
119
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2527-38
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16988940-Antineoplastic Agents,
pubmed-meshheading:16988940-Cell Line, Tumor,
pubmed-meshheading:16988940-Cisplatin,
pubmed-meshheading:16988940-Humans,
pubmed-meshheading:16988940-Neuroblastoma,
pubmed-meshheading:16988940-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:16988940-Receptor, IGF Type 1,
pubmed-meshheading:16988940-Signal Transduction
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pubmed:year |
2006
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pubmed:articleTitle |
Protein kinase B modulates the sensitivity of human neuroblastoma cells to insulin-like growth factor receptor inhibition.
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pubmed:affiliation |
Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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