Abstract
Purpose: To investigate the capacity for ZD6474, a small molecule tyrosine kinase inhibitor, to enhance antitumor and anti-metastasis effects of radiation on human nasopharyngeal carcinoma (NPC). Experimental Design: NPC cell lines and xenograft models were evaluated following treatment with ZD6474 and radiation alone and in combination compared with untreated control mice. Results: Treatment with ZD6474 enhanced the anti-proliferative effect of radiation on NPC cell lines as detected by cell proliferation and apoptosis assays. ZD6474 also induced a significant increase in the radiosensitivity of NPC cells, with radiation enhancement ratios (RERs) ranging from 1.2 to 1.6. Despite the cytotoxicity exhibited by NPC cells following radiotherapy, the invasion and migration of NPC cells were found to be unaffected. In contrast, treatment with ZD6474 strongly inhibited the invasion and migration of NPC cells. When the administration of radiation and ZD6474 was investigated in vitro, the ability of ZD6474 to inhibit activation of the pro-survival signaling pathways induced by radiation was demonstrated. In vivo, ZD6474 significantly enhanced the anti-metastasis effects of radiation, while treatment with radiation and ZD6474 was found to be well tolerated and resulted in a strong inhibition of tumor growth. Conclusions: Our results suggest the combination of radiation and ZD6474 represents a promising strategy for the treatment of human NPC.
Keywords: Anti-tumor, anti-metastasis, radiation, ZD6474, epidermal growth factor receptor, vascular endothelial growth factor receptor-2, enhancement effect, nasopharyngeal carcinoma
Current Cancer Drug Targets
Title: ZD6474, a Small Molecule Tyrosine Kinase Inhibitor, Potentiates the Anti-Tumor and Anti-Metastasis Effects of Radiation for Human Nasopharyngeal Carcinoma
Volume: 10 Issue: 6
Author(s): S. Yang, J. Wu, Y. Zuo, L. Tan, H. Jia, H. Yan, X. Zhu, M. Zeng, J. Ma and W. Huang
Affiliation:
Keywords: Anti-tumor, anti-metastasis, radiation, ZD6474, epidermal growth factor receptor, vascular endothelial growth factor receptor-2, enhancement effect, nasopharyngeal carcinoma
Abstract: Purpose: To investigate the capacity for ZD6474, a small molecule tyrosine kinase inhibitor, to enhance antitumor and anti-metastasis effects of radiation on human nasopharyngeal carcinoma (NPC). Experimental Design: NPC cell lines and xenograft models were evaluated following treatment with ZD6474 and radiation alone and in combination compared with untreated control mice. Results: Treatment with ZD6474 enhanced the anti-proliferative effect of radiation on NPC cell lines as detected by cell proliferation and apoptosis assays. ZD6474 also induced a significant increase in the radiosensitivity of NPC cells, with radiation enhancement ratios (RERs) ranging from 1.2 to 1.6. Despite the cytotoxicity exhibited by NPC cells following radiotherapy, the invasion and migration of NPC cells were found to be unaffected. In contrast, treatment with ZD6474 strongly inhibited the invasion and migration of NPC cells. When the administration of radiation and ZD6474 was investigated in vitro, the ability of ZD6474 to inhibit activation of the pro-survival signaling pathways induced by radiation was demonstrated. In vivo, ZD6474 significantly enhanced the anti-metastasis effects of radiation, while treatment with radiation and ZD6474 was found to be well tolerated and resulted in a strong inhibition of tumor growth. Conclusions: Our results suggest the combination of radiation and ZD6474 represents a promising strategy for the treatment of human NPC.
Export Options
About this article
Cite this article as:
Yang S., Wu J., Zuo Y., Tan L., Jia H., Yan H., Zhu X., Zeng M., Ma J. and Huang W., ZD6474, a Small Molecule Tyrosine Kinase Inhibitor, Potentiates the Anti-Tumor and Anti-Metastasis Effects of Radiation for Human Nasopharyngeal Carcinoma, Current Cancer Drug Targets 2010; 10 (6) . https://dx.doi.org/10.2174/156800910791859506
DOI https://dx.doi.org/10.2174/156800910791859506 |
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
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
Unraveling the Tumor Microenvironment and Potential Therapeutic Targets: Insights from Single-Cell Sequencing and Spatial Transcriptomics
This special issue will focus on unraveling the complexities of the tumor microenvironment (TME) and identifying key biomarkers for potential therapeutic targets using advanced multi-omics techniques, such as single-cell sequencing and spatial transcriptomics. We seek original research and comprehensive reviews that investigate the heterogeneity and dynamics of the TME, emphasizing ...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
-
Importance of Aquaporins in the Physiopathology of Brain Edema
Current Pharmaceutical Design Molecular Analysis of the In Vivo Metabolism and Biodistribution of Metabolically and Non-Metabolically Activated Combi-Molecules of the Triazene Class
Drug Metabolism Letters Sphingosine Kinases Signalling in Carcinogenesis
Mini-Reviews in Medicinal Chemistry NAD+ Metabolism and NAD+-Dependent Enzymes: Promising Therapeutic Targets for Neurological Diseases
Current Drug Targets Insight to Physiology and Pathology of Zinc(II) Ions and Their Actions in Breast and Prostate Carcinoma
Current Medicinal Chemistry Current Status and Perspectives in Peptide Receptor Radiation Therapy
Current Pharmaceutical Design Interlocked Systems in Nanomedicine
Current Topics in Medicinal Chemistry MicroRNA and Cancer: Tiny Molecules with Major Implications
Current Genomics Novel Biomarkers of microRNAs in Gastric Cancer: An Overview from Diagnosis to Treatment
MicroRNA Immunoregulatory and Effector Activities of Nitric Oxide and Reactive Nitrogen Species in Cancer
Current Medicinal Chemistry The Need for Calcium Channels in Cell Proliferation
Recent Patents on Anti-Cancer Drug Discovery β-Lactone Derivatives and Their Anticancer Activities: A Short Review
Current Topics in Medicinal Chemistry Patent Selections :
Recent Patents on CNS Drug Discovery (Discontinued) Synthesis and Biological Evaluation of Triazole-Vanillin Molecular Hybrids as Anti-Cancer Agents
Current Bioactive Compounds Nerve Growth Factor Receptors and Signaling in Breast Cancer
Current Cancer Drug Targets Applications of Nanomaterials for Cancer Treatment: Recent Patents Review
Recent Patents on Nanomedicine Metabolic Features of Melanoma: A Gold Mine of New Therapeutic Targets?
Current Cancer Drug Targets TGF-ß / Smad Signaling in Prostate Cancer
Current Drug Targets Current Drug Targets for Modulating Alzheimer's Amyloid Precursor Protein: Role of Specific Micro-RNA Species
Current Medicinal Chemistry Cannabinoids as Neuroprotective Agents in Traumatic Brain Injury
Current Pharmaceutical Design