Abstract
MGMT plays a key role in many kinds of cancers. However, the molecular mechanisms of MGMT involvement in gastric cancer (GC) are poorly elucidated. Here, we investigated the role of MGMT in GC cell migration, invasion and metastatic potential. Our data showed that MGMT expression was negatively correlated with lymph node metastasis and late TNM stages. These findings were accompanied by downregulation of matrix metalloproteinase 2 (MMP2). Loss of MGMT expression induced increases in GC cell metastasis and invasion potential in vitro and in vivo. These effects were reversed by inhibition of MGMT and MMP2. MGMT overexpression downregulated MMP2 protein levels, whereas this effect was counteracted by MGMT siRNA. In summary, MGMT is involved in gastric carcinogenesis via downregulation of MMP2. The MGMT/MMP2 pathway plays an essential role in GC metastasis and may be a potential therapeutic target for GC treatment.
Keywords: MGMT, MMP2, gastric carcinoma, migration, invasion, metastasis.
Anti-Cancer Agents in Medicinal Chemistry
Title:O-6-methylguanine-DNA Methyltransferase Inhibits Gastric Carcinoma Cell Migration and Invasion by Downregulation of Matrix Metalloproteinase 2
Volume: 16 Issue: 9
Author(s): Chenglong Li, Li Deng, Hugang Shen, Qingyou Meng, Aimin Qian, Hongfei Sang, Jiazeng Xia and Xiaoqiang Li
Affiliation:
Keywords: MGMT, MMP2, gastric carcinoma, migration, invasion, metastasis.
Abstract: MGMT plays a key role in many kinds of cancers. However, the molecular mechanisms of MGMT involvement in gastric cancer (GC) are poorly elucidated. Here, we investigated the role of MGMT in GC cell migration, invasion and metastatic potential. Our data showed that MGMT expression was negatively correlated with lymph node metastasis and late TNM stages. These findings were accompanied by downregulation of matrix metalloproteinase 2 (MMP2). Loss of MGMT expression induced increases in GC cell metastasis and invasion potential in vitro and in vivo. These effects were reversed by inhibition of MGMT and MMP2. MGMT overexpression downregulated MMP2 protein levels, whereas this effect was counteracted by MGMT siRNA. In summary, MGMT is involved in gastric carcinogenesis via downregulation of MMP2. The MGMT/MMP2 pathway plays an essential role in GC metastasis and may be a potential therapeutic target for GC treatment.
Export Options
About this article
Cite this article as:
Li Chenglong, Deng Li, Shen Hugang, Meng Qingyou, Qian Aimin, Sang Hongfei, Xia Jiazeng and Li Xiaoqiang, O-6-methylguanine-DNA Methyltransferase Inhibits Gastric Carcinoma Cell Migration and Invasion by Downregulation of Matrix Metalloproteinase 2, Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (9) . https://dx.doi.org/10.2174/1871520615666150914114455
DOI https://dx.doi.org/10.2174/1871520615666150914114455 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
-
Nanoformulations of Coumarins and the Hybrid Molecules of Coumarins with Potential Anticancer Effects
Anti-Cancer Agents in Medicinal Chemistry Using Cell Cultures for the Investigation of Treatments for Attention Deficit Hyperactivity Disorder: A Systematic Review
Current Neuropharmacology Probiotics: An Emerging Therapy
Current Pharmaceutical Design Pharmacogenetics of Drug Transporters and Its Impact on the Pharmacotherapy
Current Topics in Medicinal Chemistry Drugs of Abuse: Epigenetic Mechanisms in Toxicity and Addiction
Current Medicinal Chemistry Organic Antifungal Drugs and Targets of Their Action
Current Topics in Medicinal Chemistry Role of microRNAs on Blood Brain Barrier Dysfunction in Vascular Cognitive Impairment
Current Drug Delivery Isolation and Structural Elucidation of Antioxidant Peptides from Oyster (Saccostrea cucullata) Protein Hydrolysate
Protein & Peptide Letters Structure-Function Relationships in the Interaction Between the Urokinase- Type Plasminogen Activator and Its Receptor
Current Pharmaceutical Design Small Molecule Inhibitors of Multidrug Resistance Gene (MDR1) Expression: Preclinical Evaluation and Mechanisms of Action
Current Cancer Drug Targets Antioxidant Effects of Natural Bioactive Compounds
Current Pharmaceutical Design Extra Virgin Olive Oils Polyphenols: Biological Activities
Current Pharmaceutical Design Methodologies for Investigating Natural Medicines for the Treatment of Nonalcoholic Fatty Liver Disease (NAFLD)
Current Pharmaceutical Biotechnology Role of Dietary Fiber and Short-Chain Fatty Acids in the Colon
Current Pharmaceutical Design Zebrafish as a Model System to Screen Radiation Modifiers
Current Genomics Meet Our Editorial Board Member
The Natural Products Journal Fighting Diabetes: Lessons from Xenotransplantation and Nanomedicine
Current Pharmaceutical Design MicroRNA-212-3p Attenuates Neuropathic Pain via Targeting Sodium Voltage-gated Channel Alpha Subunit 3 (NaV 1.3)
Current Neurovascular Research Somatostatin: A Hormone for the Heart?
Current Vascular Pharmacology Insects Antiviral and Anticancer Peptides: New Leads for the Future?
Protein & Peptide Letters