Abstract
Pokemon gene has crucial but versatile functions in cell differentiation, proliferation and tumorigenesis. It is a master regulator of the ARF-HDM2-p53 and Rb-E2F pathways. The facts that the expression of Pokemon is essential for tumor formation and many kinds of tumors over-express the Pokemon gene make it an attractive target for therapeutic intervention for cancer treatment. In this study, we used an RNAi strategy to silence the Pokemon gene in a cervical cancer model. To address the issues involving tumor specific delivery and durable expression of siRNA, we applied the Arg-Gly-Asp (RGD) peptide ligand and polylysine (K18) fusion peptide to encapsulate a recombinant retrovirus plasmid expressing a siRNA targeting the Pokemon gene and produced the ‘mimoretrovirus’. At charge ratio 2.0 of fusion peptide/plasmid, the mimoretrovirus formed stable and homogenous nanoparticles, and provided complete DNase I protection and complete gel retardation. This nanoparticle inhibited SiHa cell proliferation and invasion, while it promoted SiHa cell apoptosis. The binding of the nanoparticle to SiHa cells was mediated via the RGD-integrin αvβ3 interaction, as evidenced by the finding that unconjugated RGD peptide inhibited this binding significantly. This tumor-targeting mimoretrovirus exhibited excellent anti-tumor capacity in vivo in a nude mouse model. Moreover, the mimoretrovirus inhibited tumor growth with a much higher efficiency than recombinant retrovirus expressing siRNA or the K18/P4 nanoparticle lacking the RGD peptide. Results suggest that the RNAi/RGD-based mimoretrovirus developed in this study represents a novel anti-tumor strategy that may be applicable to most research involving cancer therapy and, thus, has promising potential as a cervical cancer treatment.
Keywords: Pokemon, tumor-targeting, mimoretrovirus, siRNA, RGD peptide.
Current Cancer Drug Targets
Title:Tumor-Targeted Inhibition by a Novel Strategy - Mimoretrovirus Expressing siRNA Targeting the Pokemon Gene
Volume: 10 Issue: 8
Author(s): Z. Tian, H. Wang, Z. Jia, J. Shi, J. Tang, L. Mao, H. Liu, Y. Deng, Y. He, Z. Ruan, J. Li, Y. Wu and B. Ni
Affiliation:
Keywords: Pokemon, tumor-targeting, mimoretrovirus, siRNA, RGD peptide.
Abstract: Pokemon gene has crucial but versatile functions in cell differentiation, proliferation and tumorigenesis. It is a master regulator of the ARF-HDM2-p53 and Rb-E2F pathways. The facts that the expression of Pokemon is essential for tumor formation and many kinds of tumors over-express the Pokemon gene make it an attractive target for therapeutic intervention for cancer treatment. In this study, we used an RNAi strategy to silence the Pokemon gene in a cervical cancer model. To address the issues involving tumor specific delivery and durable expression of siRNA, we applied the Arg-Gly-Asp (RGD) peptide ligand and polylysine (K18) fusion peptide to encapsulate a recombinant retrovirus plasmid expressing a siRNA targeting the Pokemon gene and produced the ‘mimoretrovirus’. At charge ratio 2.0 of fusion peptide/plasmid, the mimoretrovirus formed stable and homogenous nanoparticles, and provided complete DNase I protection and complete gel retardation. This nanoparticle inhibited SiHa cell proliferation and invasion, while it promoted SiHa cell apoptosis. The binding of the nanoparticle to SiHa cells was mediated via the RGD-integrin αvβ3 interaction, as evidenced by the finding that unconjugated RGD peptide inhibited this binding significantly. This tumor-targeting mimoretrovirus exhibited excellent anti-tumor capacity in vivo in a nude mouse model. Moreover, the mimoretrovirus inhibited tumor growth with a much higher efficiency than recombinant retrovirus expressing siRNA or the K18/P4 nanoparticle lacking the RGD peptide. Results suggest that the RNAi/RGD-based mimoretrovirus developed in this study represents a novel anti-tumor strategy that may be applicable to most research involving cancer therapy and, thus, has promising potential as a cervical cancer treatment.
Export Options
About this article
Cite this article as:
Tian Z., Wang H., Jia Z., Shi J., Tang J., Mao L., Liu H., Deng Y., He Y., Ruan Z., Li J., Wu Y. and Ni B., Tumor-Targeted Inhibition by a Novel Strategy - Mimoretrovirus Expressing siRNA Targeting the Pokemon Gene, Current Cancer Drug Targets 2010; 10 (8) . https://dx.doi.org/10.2174/156800910793357907
DOI https://dx.doi.org/10.2174/156800910793357907 |
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
-
Recent Findings on the Application of Toll-like Receptors Agonists in Cancer Therapy
Current Medicinal Chemistry In Silico Studies Most Employed in the Discovery of New Antimicrobial Agents
Current Medicinal Chemistry Role of Oxygen in Cancer: Looking Beyond Hypoxia
Anti-Cancer Agents in Medicinal Chemistry Integrin-Targeted Peptide- and Peptidomimetic-Drug Conjugates for the Treatment of Tumors
Recent Patents on Anti-Cancer Drug Discovery Natural Products as Anti-Cancerous Therapeutic Molecules Targeted towards Topoisomerases
Current Protein & Peptide Science Nanocarriers Based Anticancer Drugs: Current Scenario and Future Perceptions
Current Drug Targets Recent Developments in the Applications of Palladium Complexes Bearing N-Heterocyclic Carbene Ligands
Current Organic Chemistry Expression of P-gp, MRP, LRP, GST-π and TopoIIα and Acquired Resistance to Cisplatin in Human Lung Adenocarcinoma Cells
Letters in Drug Design & Discovery Flavonoids as Anticancer Agents: Structure-Activity Relationship Study
Current Medicinal Chemistry - Anti-Cancer Agents Transplacental Antioxidants Inhibit Lung Tumors in Mice Exposed to Cigarette Smoke After Birth: A Novel Preventative Strategy?
Current Cancer Drug Targets Viral and Non-Viral Methods to Genetically Modify Dendritic Cells
Current Gene Therapy Voltage-Gated Calcium Channels as Targets for the Treatment of Chronic Pain
Current Drug Targets - CNS & Neurological Disorders Disease Progression in HIV Late Presenters: the Role of HIV Clinical Indicator Diseases Prior to HIV Diagnosis
Current HIV Research Recent Advances in Application of Poly-Epsilon-Caprolactone and its Derivative Copolymers for Controlled Release of Anti-Tumor Drugs
Current Cancer Drug Targets Multifunctional Lipoic Acid Conjugates
Current Medicinal Chemistry Utilization of Ribozymes as Antiviral Agents
Letters in Drug Design & Discovery Effects of Brain IKKβ Gene Silencing by Small Interfering RNA on P-Glycoprotein Expression and Brain Damage in the Rat Kainic Acid-Induced Seizure Model
CNS & Neurological Disorders - Drug Targets Detection of Tumor Markers with ProteinChip® Technology
Current Pharmaceutical Biotechnology Exploring Pharmacological Significance of Chalcone Scaffold: A Review
Current Medicinal Chemistry Microwave-Assisted Synthesis of Thiazole/Benzothiazole Fused Pyranopyrimidine Derivatives and Evaluation of their Biological Activity
Letters in Organic Chemistry