Abstract
The present study deals with the evaluation of the efficacy of oxaliplatin and paclitaxel combination as a potential strategy in controlling HNSCC cell proliferation and the assessment of correlation between occurrence of apoptosis and changes in expression of survivin (IAP). The panel cell lines included two HNSCC cell lines (Cal27 and NT8e) and one normal cell line (293) with differential level of survivin expression in accordance with chemosensitivity. The cytotoxicity and effect of drugs on apoptosis was determined, separately and in combination. Combined treatment of cells with paclitaxel and oxaliplatin resulted in significantly higher cytotoxicity as compared to individual single drug treatment. Cytotoxicity was prominent in paclitaxel to oxaliplatin (pacl-oxal) sequence treatment with an approximate two-fold increase in apoptosis as compared to oxaliplatin to paclitaxel (oxal-pacl) sequence treatment. Paclitaxel treatment also caused increased survivin expression showing reduced apoptosis at low concentration. Oxaliplatin, when combined with paclitaxel, decreased the survivin level with increased cell death. Inhibition of survivin by a small interfering RNA (siRNA) method also increased the sensitivity of the cancer cell lines to paclitaxel whereas over-expression of survivin in the transfected 293-cell line provided resistance. In conclusion, the interaction between drugs was synergistic and schedule-dependent. Survivin played a critical role in paclitaxel resistance through the suppression of apoptosis, and a significant induction of apoptosis was observed when oxaliplatin was combined with paclitaxel at least in part by the down-regulation of survivin.
Keywords: Survivin, oxaliplatin, paclitaxel, chemotherapy, HNSCC, apoptosis.
Current Cancer Drug Targets
Title:Oxaliplatin-mediated Inhibition of Survivin Increases Sensitivity of Head and Neck Squamous Cell Carcinoma Cell Lines to Paclitaxel
Volume: 10 Issue: 7
Author(s): Z. Khan, N. Khan, A. K. Varma, R. P. Tiwari, S. Mouhamad, G. B.K.S. Prasad and P. S. Bisen
Affiliation:
Keywords: Survivin, oxaliplatin, paclitaxel, chemotherapy, HNSCC, apoptosis.
Abstract: The present study deals with the evaluation of the efficacy of oxaliplatin and paclitaxel combination as a potential strategy in controlling HNSCC cell proliferation and the assessment of correlation between occurrence of apoptosis and changes in expression of survivin (IAP). The panel cell lines included two HNSCC cell lines (Cal27 and NT8e) and one normal cell line (293) with differential level of survivin expression in accordance with chemosensitivity. The cytotoxicity and effect of drugs on apoptosis was determined, separately and in combination. Combined treatment of cells with paclitaxel and oxaliplatin resulted in significantly higher cytotoxicity as compared to individual single drug treatment. Cytotoxicity was prominent in paclitaxel to oxaliplatin (pacl-oxal) sequence treatment with an approximate two-fold increase in apoptosis as compared to oxaliplatin to paclitaxel (oxal-pacl) sequence treatment. Paclitaxel treatment also caused increased survivin expression showing reduced apoptosis at low concentration. Oxaliplatin, when combined with paclitaxel, decreased the survivin level with increased cell death. Inhibition of survivin by a small interfering RNA (siRNA) method also increased the sensitivity of the cancer cell lines to paclitaxel whereas over-expression of survivin in the transfected 293-cell line provided resistance. In conclusion, the interaction between drugs was synergistic and schedule-dependent. Survivin played a critical role in paclitaxel resistance through the suppression of apoptosis, and a significant induction of apoptosis was observed when oxaliplatin was combined with paclitaxel at least in part by the down-regulation of survivin.
Export Options
About this article
Cite this article as:
Khan Z., Khan N., K. Varma A., P. Tiwari R., Mouhamad S., B.K.S. Prasad G. and S. Bisen P., Oxaliplatin-mediated Inhibition of Survivin Increases Sensitivity of Head and Neck Squamous Cell Carcinoma Cell Lines to Paclitaxel, Current Cancer Drug Targets 2010; 10 (7) . https://dx.doi.org/10.2174/156800910793605866
DOI https://dx.doi.org/10.2174/156800910793605866 |
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
-
Structural Basis for Therapeutic Intervention of uPA/uPAR System
Current Drug Targets Tumor Necrosis Factor: Renaissance as a Cancer Therapeutic?
Current Cancer Drug Targets The Chemopreventive Peptide Lunasin Inhibits d-Galactose- Induced Experimental Cataract in Rats
Protein & Peptide Letters Flavonoids Acting on DNA Topoisomerases: Recent Advances and Future Perspectives in Cancer Therapy
Current Medicinal Chemistry Anti-cancer Therapies in High Grade Gliomas
Current Proteomics Malignant Mesothelioma: Cell Survival Pathways and Radiation Therapy
Current Respiratory Medicine Reviews A Review of Pharmacological Treatment Options for Lung Cancer: Emphasis on Novel Nanotherapeutics and Associated Toxicity
Current Drug Targets Nutraceuticals for Promoting Longevity
Current Nutraceuticals The Role of the Antiangiogenetic Ramucirumab in the Treatment of Advanced Non Small Cell Lung Cancer
Current Medicinal Chemistry Targeting ATP7A to Increase the Sensitivity of Neuroblastoma Cells to Retinoid Therapy
Current Cancer Drug Targets Molecular Profiles of Sentinel and Non-Sentinel Lymph Nodes in Breast Cancer Progression and Prognosis
Current Cancer Therapy Reviews Genetic Variants in Genes Involved in Mechanisms of Chemoresistance to Anticancer Drugs
Current Cancer Drug Targets Identifying the Characteristics of the Hypusination Sites Using SMOTE and SVM Algorithm with Feature Selection
Current Proteomics Nuclear Factor-κB: A Holy Grail in Cancer Prevention and Therapy
Current Signal Transduction Therapy Endoglin Silencing has Significant Antitumor Effect on Murine Mammary Adenocarcinoma Mediated by Vascular Targeted Effect
Current Gene Therapy Evolution of Ipsilateral Head and Neck Radiotherapy
Current Cancer Therapy Reviews Improved Immunotoxins with Novel Functional Elements
Current Pharmaceutical Design 2-Arylbenzimidazoles as Antiviral and Antiproliferative Agents-Part 1
Medicinal Chemistry Pathways Related to the Anti-Cancer Effects of Metabolites Derived from Cerrado Biome Native Plants: An Update and Bioinformatics Analysis on Oral Squamous Cell Carcinoma
Protein & Peptide Letters Transglutaminase-Mediated Activation of Nuclear Transcription Factor-κB in Cancer Cells: A New Therapeutic Opportunity
Current Cancer Drug Targets