Targeting the insulin-like growth factor I receptor inhibits proliferation and VEGF production of non-small cell lung cancer cells and enhances paclitaxel-mediated anti-tumor effect

Lung Cancer. 2011 Aug;73(2):158-65. doi: 10.1016/j.lungcan.2010.11.010. Epub 2010 Dec 28.


The effects of AVE1642, a human monoclonal antibody against IGF-IR, were examined in NSCLC cell lines in order to characterize its anti-proliferative and anti-angiogenic activity as a single agent and in combination with chemotherapy. AVE1642 inhibited IGF-IR signaling and suppressed IGF-I-induced, serum-stimulated or autocrine-mediated proliferation of NSCLC cells in vitro. Furthermore, the combination of paclitaxel and AVE1642 resulted in a sequence-dependent increase in the inhibition of cell proliferation, compared to each agent alone, which was associated with a dose-dependent increase in phosphorylated IGF-IR and Akt. Moreover, inhibition of IGF-IR signaling by AVE1642 reduced IGF-I-induced VEGF production by NSCLC cells as well as the migratory capacity of HUVEC cells challenged with conditioned media from lung cancer cells previously exposed to IGF-I. The above results suggest that inhibition of IGF-IR signaling by AVE1642 enhances the efficacy of chemotherapy and modulates VEGF and angiogenesis in NSCLC. These effects may have important clinical implications in the treatment of NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Non-Small-Cell Lung
  • Cell Line, Tumor / drug effects
  • Cell Movement
  • Cell Proliferation / drug effects*
  • Culture Media, Conditioned
  • Drug Interactions
  • Endothelial Cells / drug effects
  • Endothelial Cells / physiology
  • Humans
  • Insulin-Like Growth Factor I / pharmacology
  • Lung Neoplasms
  • Mitogen-Activated Protein Kinases / metabolism
  • Paclitaxel / administration & dosage
  • Paclitaxel / pharmacology
  • Phosphorylation
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Receptor, IGF Type 1 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism*


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Culture Media, Conditioned
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • Mitogen-Activated Protein Kinases
  • Paclitaxel
  • AVE1642