Metformin Treatment Represses Vascular Endothelial Growth Factor Gene Transcription in MCF-7 Breast Cancer Cells

Mohamed Alalem*^1,2 and Bimal K Ray^1,2

Received: April 15, 2018;   Published: April 19, 2018

DOI: 10.32474/OAJOM.2018.01.000115

Full Text PDF

To view the Full Article   Peer-reviewed Article PDF

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.

Keywords: Metformin; mTOR; VEGF; Breast cancer

Abstract| Introduction| Materials and Methods| Results| Discussion| Conclusion| Authors’ Contributions| Funding| References|