Co-targeting IGF-1R and c-kit: synergistic inhibition of proliferation and induction of apoptosis in H 209 small cell lung cancer cells.
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.
Camirand
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Lady Davis Institute for Medical Research and Department of Oncology, McGill University, Montréal, QC, Canada.
Pollak
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D017209:Apoptosis / Q000187:drug effects; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000378:metabolism; D002455:Cell Division; D045744:Cell Line, Tumor; D004357:Drug Synergism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects*; D017526:Receptor, IGF Type 1 / Q000187:drug effects*; D020032:Tyrphostins / Q000494:pharmacology*
D020032:Tyrphostins; D019009:Proto-Oncogene Proteins c-kit; D017526:Receptor, IGF Type 1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases