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.
Keywords: Angiogenesis, combination treatment, HSP90 inhibitor, NVP-AUY922, oral squamous cell carcinoma, temsirolimus
Current Cancer Drug Targets
Title:Novel HSP90 Inhibitor NVP-AUY922 Enhances the Anti-tumor Effect of Temsirolimus Against Oral Squamous Cell Carcinoma
Volume: 13 Issue: 3
Author(s): Tatsuo Okui, Tsuyoshi Shimo, Takuya Fukazawa, Nur Mohammad Monsur Hassan, Tatsuki Honami, Soichiro Ibaragi, Munenori Takaoka, Yoshio Naomoto and Akira Sasaki
Affiliation:
Keywords: Angiogenesis, combination treatment, HSP90 inhibitor, NVP-AUY922, oral squamous cell carcinoma, temsirolimus
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.
Export Options
About this article
Cite this article as:
Okui Tatsuo, Shimo Tsuyoshi, Fukazawa Takuya, Mohammad Monsur Hassan Nur, Honami Tatsuki, Ibaragi Soichiro, Takaoka Munenori, Naomoto Yoshio and Sasaki Akira, Novel HSP90 Inhibitor NVP-AUY922 Enhances the Anti-tumor Effect of Temsirolimus Against Oral Squamous Cell Carcinoma, Current Cancer Drug Targets 2013; 13 (3) . https://dx.doi.org/10.2174/1568009611313030007
DOI https://dx.doi.org/10.2174/1568009611313030007 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Tumor Necrosis Factor: Renaissance as a Cancer Therapeutic?
Current Cancer Drug Targets The Crosstalk Between the Matrix Metalloprotease System and the Chemokine Network in Acute Myeloid Leukemia
Current Medicinal Chemistry Dual Inhibitors of PI3K/mTOR or mTOR-Selective Inhibitors: Which Way Shall We Go?
Current Medicinal Chemistry Bladder Cancer Stem Cells
Current Stem Cell Research & Therapy Novel Agents Targeting Bioactive Sphingolipids for the Treatment of Cancer
Current Medicinal Chemistry Differentiation-Inducing Therapy for Solid Tumors
Current Pharmaceutical Design MicroRNA: Biogenesis, Function and Role in Cancer
Current Genomics Obesity and Cancer: Biological Links and Treatment Implications
Current Cancer Drug Targets From Multiple PAR1 Receptor/Protein Interactions to their Multiple Therapeutic Implications
Current Topics in Medicinal Chemistry Deregulation of the Akt Pathway in Human Cancer
Current Cancer Drug Targets Iron and Iron Chelators: A Review on Potential Effects on Skin Aging
Current Aging Science Namitecan: a Hydrophilic Camptothecin with a Promising Preclinical Profile
Current Medicinal Chemistry Role of the Akt Pathway in Prostate Cancer
Current Cancer Drug Targets Latest Insights into the Anticancer Activity of Gold(III)-Dithiocarbamato Complexes
Anti-Cancer Agents in Medicinal Chemistry Progesterone Receptor Membrane Component 1 and its Accomplice: Emerging Therapeutic Targets in Lung Cancer
Endocrine, Metabolic & Immune Disorders - Drug Targets Radiologic Findings of a Rare Subtype of Invasive Breast Cancer with Poor Prognosis: Metaplastic Carcinoma of the Breast
Current Medical Imaging Targeted Therapies in Combination with Radiotherapy in Oesophageal and Gastroesophageal Carcinoma
Current Medicinal Chemistry Tubulins as Therapeutic Targets in Cancer: from Bench to Bedside
Current Pharmaceutical Design NF-κ B and Rheumatic Diseases
Endocrine, Metabolic & Immune Disorders - Drug Targets Mechanism of Cancer Drug Resistance and the Involvement of Noncoding RNAs
Current Medicinal Chemistry