title: Inhibition of IGF-1 signalling enhances the apoptotic effect of AS602868, an IKK2 inhibitor, in multiple myeloma cell lines.
abstract: Multiple myeloma (MM) is a B cell neoplasm characterized by bone marrow infiltration with malignant plasma cells. IGF-1 signalling has been explored as a therapeutic target in this disease. We analyzed the effect of the IKK2 inhibitor AS602868, in combination with a monoclonal antibody targeting IGF-1 receptor (anti-IGF-1R) in human MM cell lines. We found that anti-IGF-1R potentiated the apoptotic effect of AS602868 in LP1 and RPMI8226 MM cell lines which express high levels of IGF-1R. Anti-IGF-1R enhanced the inhibitory effect of AS602868 on NF-κB pathway signalling and potentiated the disruption of mitochondrial membrane potential caused by AS602868. These results support the role of IGF-1 signalling in MM and suggest that inhibition of this pathway could sensitize MM cells to NF-κB inhibitors.
authors.affiliation: Université de Lyon, Lyon, France.
authors.forename: Ines
authors.initials: I
authors.lastname: Tagoug
authors.forename: Amélie
authors.initials: A
authors.lastname: Sauty De Chalon
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004347:Drug Interactions; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009101:Multiple Myeloma / Q000188:drug therapy / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D017526:Receptor, IGF Type 1 / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C519899:AS602868; D000911:Antibodies, Monoclonal; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D011743:Pyrimidines; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase