Co-targeting IGF-1R and c-kit: synergistic inhibition of proliferation and induction of apoptosis in H 209 small cell lung cancer cells

Br J Cancer. 2004 May 4;90(9):1825-9. doi: 10.1038/sj.bjc.6601682.

Abstract

Most small cell lung cancers (SCLC) coexpress the c-kit protein tyrosine receptor kinase and its ligand stem cell factor, resulting in an autocrine loop. As SCLC growth is also driven by insulin-like growth factor-1 receptor (IGF-1R) signalling, tyrphostins AG 1024 and 1296 (inhibitors of IGF-1R and c-kit activity, respectively) were used to co-target these receptors in H 209 SCLC cells. Combination treatment caused synergy in proliferation inhibition and in apoptosis induction, and also enhanced reduction in phosphorylation of Erk1/Erk2, suggesting that co-targeting IGF-1R and c-kit in SCLC may be more effective than single-agent therapies.

MeSH terms

  • Apoptosis / drug effects
  • Carcinoma, Small Cell / drug therapy*
  • Carcinoma, Small Cell / metabolism
  • Cell Division
  • Cell Line, Tumor
  • Drug Synergism
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Mitogen-Activated Protein Kinase 1 / drug effects
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / drug effects
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-kit / drug effects*
  • Receptor, IGF Type 1 / drug effects*
  • Tyrphostins / pharmacology*

Substances

  • Tyrphostins
  • Proto-Oncogene Proteins c-kit
  • Receptor, IGF Type 1
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases