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Synergistic apoptosis in head and neck squamous cell carcinoma cells by co-inhibition of insulin-like growth factor-1 receptor signaling and compensatory signaling pathways.
- Source :
-
Head & neck [Head Neck] 2015 Dec; Vol. 37 (12), pp. 1722-32. Date of Electronic Publication: 2015 Apr 06. - Publication Year :
- 2015
-
Abstract
- Background: In head and neck squamous cell carcinoma (HNSCC), resistance to single-agent targeted therapy may be overcome by co-targeting of compensatory signaling pathways.<br />Methods: A targeted drug screen with 120 combinations was used on 9 HNSCC cell lines.<br />Results: Multiple novel drug combinations demonstrated synergistic growth inhibition. Combining the insulin-like growth factor-1 receptor (IGF-1R) inhibitor, BMS754807, with either the human epidermal growth factor receptor (HER)-family inhibitor, BMS599626, or the Src-family kinase inhibitor, dasatinib, resulted in substantial synergy and growth inhibition. Depending on the cell line, these combinations induced synergistic or additive apoptosis; when synergistic apoptosis was observed, AKT phosphorylation was inhibited to a greater extent than either drug alone. Conversely, when additive apoptosis occurred, AKT phosphorylation was not reduced by the drug combination.<br />Conclusion: Combined IGF-1R/HER family and IGF-1R/Src family inhibition may have therapeutic potential in HNSCC. AKT may be a node of convergence between IGF-1R signaling and pathways that compensate for IGF-1R inhibition.<br /> (© 2015 Wiley Periodicals, Inc.)
- Subjects :
- Antineoplastic Combined Chemotherapy Protocols pharmacology
Carbamates administration & dosage
Carcinoma, Squamous Cell metabolism
Cell Culture Techniques
Cell Line, Tumor
Dasatinib administration & dosage
Drug Resistance, Neoplasm
Drug Synergism
Head and Neck Neoplasms metabolism
Humans
Phosphorylation drug effects
Proto-Oncogene Proteins c-akt drug effects
Pyrazoles administration & dosage
Triazines administration & dosage
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Apoptosis drug effects
Carcinoma, Squamous Cell drug therapy
Head and Neck Neoplasms drug therapy
Proto-Oncogene Proteins c-akt metabolism
Receptor, IGF Type 1 antagonists & inhibitors
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0347
- Volume :
- 37
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Head & neck
- Publication Type :
- Academic Journal
- Accession number :
- 24986420
- Full Text :
- https://doi.org/10.1002/hed.23822