کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2195943 | 1550879 | 2015 | 8 صفحه PDF | دانلود رایگان |
• The anti-diabetic drug metformin suppressed VEGF expression in ELT-3cells.
• Metformin down-regulated HIF-1α activation at the post-translational level.
• Metformin suppressed mTORC1 activity by phosphorylating the mTORC1 component raptor.
• Metformin inhibited VEGF expression via the mTORC1/HIF-1α pathway.
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.
Journal: Molecular and Cellular Endocrinology - Volume 399, 5 January 2015, Pages 1–8