Metformin Treatment Represses Vascular Endothelial Growth Factor Gene Transcription in MCF-7 Breast Cancer Cells
Journal Title: Open Access Journal of Oncology and Medicine - Year 2018, Vol 1, Issue 3
Abstract
Background/Aim:Targeting angiogenesis preferentially in cancer is a promising approach to improve treatment efficacy and safety. The aim of this study is investigate potential upregulation of Krüppel like factor-4(KLF-4) by inhibition of mammalian target of rapamycin (mTOR) to repress vascular endothelial growth factor (VEGF) expression in breast cancer cells. Materials and Methods: Using Western blot; bandshift assay; and Chloramphenicol acetyltransferase assay, we assessed the effect of different mTOR inhibitors on the level of mTOR pathway proteins and on KLF-4/ serum amyloid activating factor (SAF-1) SAF-1 DNA binding and consequently VEGF gene expression in MCF-7breast cancer cells. Results: mTOR inhibition increased KLF-4 level in breast cancer cells, but this inhibition, except for metformin, elicited rebound upregulation of mTOR signaling proteins. Thus metformin produced a sustained increase in KLF-4 level and concomitant disruption of SAF-1 binding to VEGF promoter with consequent inhibition of VEGF expression. Conclusion:Repurposing metformin as a potential neoadjuvant and antiangiogenic treatment could provide the basis for more effective and safer antiangiogenic treatment.
Authors and Affiliations
Mohamed Alalem, Bimal K Ray
Keywords
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- EP ID EP586783
- DOI 10.32474/OAJOM.2018.01.000115
- Views 93
- Downloads 0
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