Abstract
Hepatocellular carcinoma (HCC) prognosis is very poor, its early treatment is of the utmost importance. Glypican-3 (GPC-3), a membrane-associated heparan sulfate proteoglycan, plays a crucial role in cell proliferation and metastasis, particularly in progression. GPC-3 mediated oncogenesis involves signaling pathways during the malignant transformation of hepatocyte carcinogenesis, with an increasing expression of GPC-3 observed from non-cancerous- to cancerous-tissues, with brown granule-like staining localized in tumor parts of atypical hyperplasia and HCC formation. GPC-3 expression in HCC tissues or circulating blood was associated with tumor size or HBV infection. Circulation of GPC-3-mRNA was detected in HCC patients with relation to TNM stage, periportal cancerous embolus, and extra-hepatic metastasis. After hepatoma, cells were transfected with shRNA, GPC-3 expression or proliferation was inhibited with promoting apoptosis, cell cycle arrested in G1 phase, alteration of hepatoma cell migration and invasion behaviors with down-regulation of β-catenin, IGF-II, and VEGF, and growth of nude mice xenograft tumors was significantly suppressed with the decreases in β -catenin, p-GSK3β, and cyclinD1 expression, suggesting that GPC-3 not only is a specific biomarker for HCC diagnosis, but also is a valuable molecular-target for HCC gene therapy.
Keywords: Diagnosis, glypican-3, hepatocellular carcinoma, signal pathways, targeted-therapy.
Mini-Reviews in Medicinal Chemistry
Title:Down-regulating Glypican-3 Expression: Molecular-targeted Therapy for Hepatocellular Carcinoma
Volume: 14 Issue: 14
Author(s): Zhizhen Dong, Min Yao, Li Wang, Junling Yang and Dengfu Yao
Affiliation:
Keywords: Diagnosis, glypican-3, hepatocellular carcinoma, signal pathways, targeted-therapy.
Abstract: Hepatocellular carcinoma (HCC) prognosis is very poor, its early treatment is of the utmost importance. Glypican-3 (GPC-3), a membrane-associated heparan sulfate proteoglycan, plays a crucial role in cell proliferation and metastasis, particularly in progression. GPC-3 mediated oncogenesis involves signaling pathways during the malignant transformation of hepatocyte carcinogenesis, with an increasing expression of GPC-3 observed from non-cancerous- to cancerous-tissues, with brown granule-like staining localized in tumor parts of atypical hyperplasia and HCC formation. GPC-3 expression in HCC tissues or circulating blood was associated with tumor size or HBV infection. Circulation of GPC-3-mRNA was detected in HCC patients with relation to TNM stage, periportal cancerous embolus, and extra-hepatic metastasis. After hepatoma, cells were transfected with shRNA, GPC-3 expression or proliferation was inhibited with promoting apoptosis, cell cycle arrested in G1 phase, alteration of hepatoma cell migration and invasion behaviors with down-regulation of β-catenin, IGF-II, and VEGF, and growth of nude mice xenograft tumors was significantly suppressed with the decreases in β -catenin, p-GSK3β, and cyclinD1 expression, suggesting that GPC-3 not only is a specific biomarker for HCC diagnosis, but also is a valuable molecular-target for HCC gene therapy.
Export Options
About this article
Cite this article as:
Dong Zhizhen, Yao Min, Wang Li, Yang Junling and Yao Dengfu, Down-regulating Glypican-3 Expression: Molecular-targeted Therapy for Hepatocellular Carcinoma, Mini-Reviews in Medicinal Chemistry 2014; 14 (14) . https://dx.doi.org/10.2174/1389557515666150101105135
DOI https://dx.doi.org/10.2174/1389557515666150101105135 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...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
-
Midkine in Inflammatory and Toxic Conditions
Current Drug Delivery The Adenine Nucleotide Translocator: A New Potential Chemotherapeutic Target
Current Drug Targets Modulation of Cellular Function by TAT Mediated Transduction of Full Length Proteins
Current Protein & Peptide Science The Use of DNA Microarrays to Investigate the Pharmacogenomics of Drug Response in Living Systems
Current Topics in Medicinal Chemistry Positron Emission Tomography Imaging of Tumor Hypoxia
Current Medical Imaging Short-Chain Fatty Acid Inhibitors of Histone Deacetylases: Promising Anticancer Therapeutics?
Current Cancer Drug Targets Leuckart Synthesis and Pharmacological Assessment of Novel Acetamide Derivatives
Anti-Cancer Agents in Medicinal Chemistry Bioactive Polyphenols from Healthy Diets and Forest Biomass
Current Nutrition & Food Science Discovery of Biomarkers in Hepatocellular Carcinoma Metastasis Using Bioinformatic Analysis
Current Bioinformatics Linking Inflammation to Cell Cycle Progression
Current Pharmaceutical Design Monitoring T Cell Responses to Cancer Immunotherapy: Can We Now Identify Biomarkers Predicting Patients Who will be Responders
Current Cancer Therapy Reviews Linc01559 Served as a Potential Oncogene and Promoted Resistance of Hepatocellular Carcinoma to Oxaliplatin by Directly Sponging miR-6783-3p
Anti-Cancer Agents in Medicinal Chemistry Nano Drug Delivery in Treatment of Oral Cancer, A Review of the Literature
Current Drug Targets Micro-CT Assessments of Potential Anti-Osteoporotic Agents
Current Drug Targets p53-Induced Apoptosis and Inhibitors of p53
Current Medicinal Chemistry Phycobilins and Phycobiliproteins Used in Food Industry and Medicine
Mini-Reviews in Medicinal Chemistry Pharmacologic Activation of p53 by Small-Molecule MDM2 Antagonists
Current Pharmaceutical Design Withdrawal Notice: Emerging Biomarkers and Contributing Factors of Prostate Cancer
Current Cancer Therapy Reviews A Century of Thioxanthones: Through Synthesis and Biological Applications
Current Medicinal Chemistry Stem Cell Research and Therapy for Liver Disease
Current Stem Cell Research & Therapy