Abstract
The use of adult stem cells as gene delivery vehicles is a novel and attractive strategy for cancer therapy. Mesenchymal stem cells (MSCs) provide a promising source for stem cell-based gene therapies. Interleukin-24 (IL24) has been suggested as an effective anticancer agent. However, a lack of tumor-targeted delivery and a host immune response to viral vehicles has hindered its application for cancer therapy. In this study, we evaluated the effects of IL24 delivered by MSCs as a therapeutic approach for lung cancer. We engineered human umbilical cord-derived MSCs (UC-MSCs) to efficiently deliver secretable IL24. We observed that IL24-transduced UC-MSCs (IL24-MSCs) inhibited the growth of A549 lung cancer cells by induction of apoptosis and cell cycle arrest. The IL24 proteins secreted by IL24-MSCs were involved in regulating the ERK-1/2, AKT and JNK signaling pathways. Additionally, MSCs-mediated IL24 expression led to an increase in the cleavage of caspases-3/8/9 and PARP, the Bax/Bcl-2 ratio, as well as the p21 expression in A549 cells. We also demonstrated that injection of IL24-MSCs significantly suppressed xenograft tumor growth. Moreover, the IL24-MSCs had anti-angiogenic effects both in vitro and in vivo. Taken together, our findings indicate that IL24 delivered by human UC-MSCs has the potential to be used as an alternative strategy for lung cancer therapy.
Keywords: Cancer therapy, interleukin-24, mesenchymal stem cells, targeted delivery
Current Cancer Drug Targets
Title:Experimental Therapy for Lung Cancer: Umbilical Cord-Derived Mesenchymal Stem Cell-Mediated Interleukin-24 Delivery
Volume: 13 Issue: 1
Author(s): Xu Zhang, Leilei Zhang, Wenrong Xu, Hui Qian, Shengqin Ye, Wei Zhu, Hongcui Cao, Yongmin Yan, Wei Li, Mei Wang, Wei Wang and Ruiwen Zhang
Affiliation:
Keywords: Cancer therapy, interleukin-24, mesenchymal stem cells, targeted delivery
Abstract: The use of adult stem cells as gene delivery vehicles is a novel and attractive strategy for cancer therapy. Mesenchymal stem cells (MSCs) provide a promising source for stem cell-based gene therapies. Interleukin-24 (IL24) has been suggested as an effective anticancer agent. However, a lack of tumor-targeted delivery and a host immune response to viral vehicles has hindered its application for cancer therapy. In this study, we evaluated the effects of IL24 delivered by MSCs as a therapeutic approach for lung cancer. We engineered human umbilical cord-derived MSCs (UC-MSCs) to efficiently deliver secretable IL24. We observed that IL24-transduced UC-MSCs (IL24-MSCs) inhibited the growth of A549 lung cancer cells by induction of apoptosis and cell cycle arrest. The IL24 proteins secreted by IL24-MSCs were involved in regulating the ERK-1/2, AKT and JNK signaling pathways. Additionally, MSCs-mediated IL24 expression led to an increase in the cleavage of caspases-3/8/9 and PARP, the Bax/Bcl-2 ratio, as well as the p21 expression in A549 cells. We also demonstrated that injection of IL24-MSCs significantly suppressed xenograft tumor growth. Moreover, the IL24-MSCs had anti-angiogenic effects both in vitro and in vivo. Taken together, our findings indicate that IL24 delivered by human UC-MSCs has the potential to be used as an alternative strategy for lung cancer therapy.
Export Options
About this article
Cite this article as:
Zhang Xu, Zhang Leilei, Xu Wenrong, Qian Hui, Ye Shengqin, Zhu Wei, Cao Hongcui, Yan Yongmin, Li Wei, Wang Mei, Wang Wei and Zhang Ruiwen, Experimental Therapy for Lung Cancer: Umbilical Cord-Derived Mesenchymal Stem Cell-Mediated Interleukin-24 Delivery, Current Cancer Drug Targets 2013; 13 (1) . https://dx.doi.org/10.2174/1568009611309010092
DOI https://dx.doi.org/10.2174/1568009611309010092 |
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
-
Curcumin in Combined Cancer Therapy
Current Pharmaceutical Design Phytochemicals and Cancer Stem Cells: A Pancreatic Cancer Overview
Current Chemical Biology The Role of CXC-Chemokine IL-8, IL-6 and CXCR2 Receptor in Lymphoplasmacytic Lymphoma: Correlations with Microvascular Characteristics and Clinical Features
Current Angiogenesis (Discontinued) Recent Advances in Epitope Design for Immunotherapy of Cancer
Recent Patents on Anti-Cancer Drug Discovery Recent Progress on Chemical Biology of Pluripotent Stem Cell Selfrenewal, Reprogramming and Cardiomyogenesis
Recent Patents on Regenerative Medicine Development of Decision Tree Models for Substrates, Inhibitors, and Inducers of P-Glycoprotein
Current Drug Metabolism Reconstruction, Topological and Gene Ontology Enrichment Analysis of Cancerous Gene Regulatory Network Modules
Current Bioinformatics Endoglin Silencing has Significant Antitumor Effect on Murine Mammary Adenocarcinoma Mediated by Vascular Targeted Effect
Current Gene Therapy Editorial (Thematic Issue: Advances in Drug Discovery for the Treatment of Cancer: Many Approaches, One Goal)
Current Topics in Medicinal Chemistry Mechanisms Involved in Apoptosis Events Contributing to Sepsis-Induced Myocardial Dysfunction
Current Drug Therapy TGFb and its Smad Connection to Cancer
Current Genomics The Application of Fungal Beta-glucans for the Treatment of Colon Cancer
Anti-Cancer Agents in Medicinal Chemistry Graphical Abstracts:
Current Nanoscience Small Non-Coding RNAs as Novel Therapeutics
Current Molecular Medicine The Metabolism of Anticancer Drugs by the Liver: Current Approaches to the Drug Development Process
Current Drug Metabolism Novel Agents in the Management of Lung Cancer
Current Medicinal Chemistry Glutamine, Glucose and other Fuels for Cancer
Current Pharmaceutical Design Identification of VEGFR2-Binding Peptides Using High Throughput Bacterial Display Methods and Functional Assessment
Current Cancer Drug Targets Synthetic Hammerhead Ribozymes as Therapeutic Tools to Control Disease Genes
Current Gene Therapy Methionine AminoPeptidase Type-2 Inhibitors Targeting Angiogenesis
Current Topics in Medicinal Chemistry