Effect of metformin on the proliferation, migration, and MMP-2 and-9 expression of human umbilical vein endothelial cells
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Recent epidemiological studies have demonstrated that metformin lowers the risk of several types of cancer in diabetic patients. Matrix metalloproteinases (MMPs) play a crucial role in the degradation of the vascular basement membrane extracellular matrix proteins, thereby promoting endothelial cell invasion, migration and angiogenesis in the incidence and progression of tumors. The aim of this study was to investigate the effects of metformin on human umbilical vein endothelial cell (HUVEC) proliferation and migration, as well as on MMP-2 and MMP-9 expression. Cell proliferation was determined by cell counting and MTT colorimetric assays. Cell migration was assessed by the wound repair method. Quantitative real-time reverse transcription PCR was performed to quantify the mRNA expression of MMPs. Metformin at concentrations of 0.5-3.0 mM effectively reduced the number of endothelial cells by 5.5-55%, without being cytotoxic to the cells. Similarly, cell proliferation and migration were markedly inhibited by metformin. In addition, treatment with metformin demonstrated a strong (P<0.001) suppressive effect on the mRNA levels of MMP-2 and -9 in the endothelial cells. The inhibitory effects of metformin on endothelial cell number, migration, and MMP expression were reversed partially by compound C, which is an inhibitor of AMP-activated protein kinase (AMPK). The present study reports that metformin considerably inhibited the proliferation, migration, and MMP-2 and -9 expression of HUVECs, and the effect was partially AMPK-dependent. The obtained findings provide a molecular rationale, whereby metformin can exert anticancer effects.
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Animal studies in FXS have demonstrated a hyperactive insulin receptor and up-regulation of mTORC1 and MAPK/ERK signaling pathways, as well as elevation of MMP-9 levels in the absence of FMRP.
“Animal studies in FXS have demonstrated a hyperactive insulin receptor and up-regulation of the mammalian target of rapamycin complex 1 (mTORC1) and mitogen-activated protein kinase/extracellular signal-related kinases (MAPK/ERK) signaling pathways, as well as elevation of MMP-9 levels in the absence of FMRP, the protein produced by the FMR1 gene [106–108].”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [108]
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- Authors
- ESFAHANIAN, N., SHAKIBA, Y., NIKBIN, B., SORAYA, H., MALEKI-DIZAJI, N., GHAZI-KHANSARI, M., & GARJANI, A.
- Affiliations
- Tabriz University of Medical Sciences (IR)
- Tehran University of Medical Sciences (IR)
- Corresponding author
- GARJANI, ALIREZA
- Venue
- Molecular Medicine Reports
- Publisher
- Spandidos Publications
- Published
- 2012-01-12
- Volume
- 5
- Issue
- 4
- Pages
- 1068-1074
- ISSN
- 1791-2997 (ISSN-L)
- 1791-3004
- PMC
- PMC3493092
- OpenAlex
- W2037187996
- Cited by
- 120
- References
- 46
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 15 · 2022: 4 · 2021: 15 · 2020: 11 · 2019: 16 · 2018: 9 · 2017: 17 · 2016: 5 · 2015: 11 · 2014: 4 · 2013: 4 · 2012: 3
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Medicine Reports (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Tabriz University of Medical Sciences
- Tehran University of Medical Sciences and Health Services
- University of Tabriz
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- metformin, human umbilical vein endothelial cells, endothelial cell proliferation, endothelial cell migration, MMP-2, MMP-9, matrix metalloproteinases, AMPK, compound C, angiogenesis, anticancer effects, diabetes mellitus
- MeSH terms
- Cell Movement, Humans, Hypoglycemic Agents, Metformin, Pyrazoles, Pyrimidines, Gene Expression Regulation, Enzymologic, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Cell Proliferation, AMP-Activated Protein Kinases, Human Umbilical Vein Endothelial Cells
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