RRC ID 44075
Author Okui T, Shimo T, Fukazawa T, Mohammad Monsur Hassan N, Honami T, Ibaragi S, Takaoka M, Naomoto Y, Sasaki A.
Title Novel HSP90 inhibitor NVP-AUY922 enhances the anti-tumor effect of temsirolimus against oral squamous cell carcinoma.
Journal Curr Cancer Drug Targets
Abstract BACKGROUND AND AIM:Heat shock protein 90 (HSP90) and mammalian target of rapamycin (mTOR) are involved in the molecular pathogenesis of advanced oral squamous cell carcinoma. HSP90 inhibitors are capable of effectively interfering with multiple signaling pathways, including the mTOR signaling pathway. However, the combined effects of HSP90 and mTOR inhibitors on oral squamous cell carcinoma are still unknown. In this study, we investigated the dual treatment of the novel HSP90 inhibitor NVP-AUY922 and temsirolimus against oral squamous cell carcinoma.
MATERIALS AND METHODS:The effect of the combination of NVP-AUY922 and temsirolimus on oral squamous cell carcinoma in vitro and in vivo was determined by MTS assay and mouse xenograft models. The effect of the combination on angiogenesis was determined by tube formation assay and angioreactor.
RESULTS:The combination treatment of NVP-AUY922 and temsirolimus significantly inhibited the proliferation of SAS oral squamous cell carcinoma cells in vitro and suppressed the growth of oral squamous cell carcinoma xenografts in vivo. We have clearly shown that the combination treatment of NVP-AUY922 and temsirolimus inhibited vascular formation both in vitro and in vivo. Moreover, the combination treatment of NVP-AUY922 and temsirolimus prolonged the survival rate in mice xenografted with oral squamous cell carcinoma.
CONCLUSIONS:Here, we showed the activity of a combination of mTOR and HSP90 inhibitors for the treatment of advanced oral squamous carcinoma.
Volume 13(3)
Pages 289-99
Published 2013-3
DOI 10.2174/1568009611313030007
PII CCDT-EPUB-20120917-1
PMID 23016912
MeSH Angiogenesis Inhibitors / administration & dosage Angiogenesis Inhibitors / pharmacology Angiogenesis Inhibitors / therapeutic use Animals Antineoplastic Combined Chemotherapy Protocols / administration & dosage Antineoplastic Combined Chemotherapy Protocols / pharmacology Antineoplastic Combined Chemotherapy Protocols / therapeutic use* Carcinoma, Squamous Cell / blood supply Carcinoma, Squamous Cell / drug therapy* Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology Cell Line, Tumor Cells, Cultured Female HSP90 Heat-Shock Proteins / antagonists & inhibitors* HSP90 Heat-Shock Proteins / metabolism Head and Neck Neoplasms / blood supply Head and Neck Neoplasms / drug therapy Head and Neck Neoplasms / metabolism Head and Neck Neoplasms / pathology Human Umbilical Vein Endothelial Cells / cytology Human Umbilical Vein Endothelial Cells / drug effects Human Umbilical Vein Endothelial Cells / metabolism Humans Isoxazoles / administration & dosage Isoxazoles / pharmacology Isoxazoles / therapeutic use* Mice Mice, Nude Molecular Targeted Therapy Mouth Neoplasms / blood supply Mouth Neoplasms / drug therapy* Mouth Neoplasms / metabolism Mouth Neoplasms / pathology Neoplasm Proteins / antagonists & inhibitors Neoplasm Proteins / metabolism Neovascularization, Pathologic / drug therapy Neovascularization, Pathologic / metabolism Neovascularization, Pathologic / pathology Protein Kinase Inhibitors / administration & dosage Protein Kinase Inhibitors / pharmacology Protein Kinase Inhibitors / therapeutic use Random Allocation Resorcinols / administration & dosage Resorcinols / pharmacology Resorcinols / therapeutic use* Sirolimus / administration & dosage Sirolimus / analogs & derivatives* Sirolimus / pharmacology Sirolimus / therapeutic use Squamous Cell Carcinoma of Head and Neck TOR Serine-Threonine Kinases / antagonists & inhibitors* Xenograft Model Antitumor Assays
IF 2.626
Times Cited 4
Human and Animal Cells