Protein kinase B modulates the sensitivity of human neuroblastoma cells to insulin-like growth factor receptor inhibition

摘要: 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 a panel cell lines inhibited by with IC50 values ranging from 0.15 to 5 μM. Experiments using IGF-IR neutralizing antibody confirmed that essential support lines. expression levels individual did not correlate sensitivities NVP-AEW541, while coexpression and insulin (IR) correlated lower sensitivity some Intriguingly, high activation Akt/protein kinase B (PKB) phosphorylation ribosomal S6 protein were observed decreased NVP-AEW541. Inhibition Akt/PKB activity restored cells inhibitor. Transfection activated Akt or (S6K) IGF-I-stimulated proliferation completely blocked combination phosphoinositide 3-kinase rapamycin. In addition its effects, sensitized cisplatin-induced apoptosis. Together, our data demonstrate inhibitors chemotherapeutic agents may represent approach target proliferation. © 2006 Wiley-Liss, Inc.