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
-
Targeting Cancer Stem Cells with Natural Products
Current Drug Targets Topical Dermatological Drug Delivery: Quo Vadis?
Current Drug Delivery MicroRNAs and Cancer; an Overview
Current Pharmaceutical Biotechnology Harmine Induces Gastric Cancer Cell Apoptosis through the ROSmediated PI3K/AKT Signaling Pathway
Current Signal Transduction Therapy Adipose Tissue in the Regulation of Inflammation
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Structure, Function, Involvement in Diseases and Targeting of 14-3-3 Proteins: An Update
Current Medicinal Chemistry The Use of Auxiliary Agents to Improve the Mucosal Uptake of Peptides
Medicinal Chemistry Reviews - Online (Discontinued) Mitochondrial VDAC1: Function in Cell Life and Death and a Target for Cancer Therapy
Current Medicinal Chemistry Surface Markers of Cancer Stem Cells in Solid Tumors
Current Stem Cell Research & Therapy Nanoparticles based on oleate alginate ester as curcumin delivery system
Current Drug Delivery Recent Progress in Graphene Derivatives/Metal Oxides Binary Nanocomposites Based Chemi-resistive Sensors for Disease Diagnosis by Breath Analysis
Current Analytical Chemistry Recent Patents on Antibacterial, Antifungal and Antiviral Properties of Tea
Recent Patents on Anti-Infective Drug Discovery Smart Stimuli Sensitive Nanogels in Cancer Drug Delivery and Imaging: A Review
Current Pharmaceutical Design Selective Inhibition of Osteoclast Vacuolar H+-ATPase
Current Pharmaceutical Design Pre-feasibility Study for Establishing Radioisotope and Radiopharmaceutical Production Facilities in Developing Countries
Current Radiopharmaceuticals Development of Focal Adhesion Kinase Inhibitors in Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry PI-3-Kinase Inhibitors in Colorectal Cancer
Current Cancer Drug Targets Mitochondria as Possible Pharmaceutical Targets for the Effects of Vitamin E and its Homologues in Oxidative Stress-Related Diseases
Current Pharmaceutical Design Targeted Alpha Therapy with 213Bi
Current Radiopharmaceuticals Extrinsic Factors Promoting Insulin Producing Cell-Differentiation and Insulin Expression Enhancement-Hope for Diabetics.
Current Stem Cell Research & Therapy