Abstract
The aim of this study was to elucidate whether metformin can regulate the expression of vascular endothelial growth factor (VEGF) in rat-derived uterine leiomyoma cells (ELT-3 cells). In vitro studies were conducted using ELT-3 cells. Under normoxic conditions, metformin suppressed VEGF protein levels in the supernatant and cells in a dose-dependent manner. In hypoxia-mimicking conditions, VEGF and hypoxia-inducible factor-1α (HIF-1α) proteins were both highly expressed and were suppressed by the metformin treatment. Metformin did not affect HIF-1α mRNA levels, which indicated that its effects occurred at the post-translational level. Metformin inhibited mammalian target of rapamycin complex 1 (mTORC1) activity by phosphorylating the mTORC1 component raptor. This study revealed the anti-angiogenic activity of metformin in ELT-3 cells by suppressing the expression of VEGF via the mTORC1/HIF-1α pathway. These results indicate that metformin may represent an effective alternative in the future treatment of uterine leiomyomas.
Original language | English |
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Pages (from-to) | 1-8 |
Number of pages | 8 |
Journal | Molecular and Cellular Endocrinology |
Volume | 399 |
DOIs | |
Publication status | Published - 2015 Jan 5 |
Keywords
- Angiogenesis
- HIF-1α
- MTOR
- Metformin
- Uterine leiomyoma
- VEGF
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Endocrinology