Research Paper Volume 11, Issue 10 pp 3198—3219

Simvastatin induces breast cancer cell death through oxidative stress up-regulating miR-140-5p

Fuliang Bai1, *,, Ze Yu2, *,, Xin Gao3, , Jiawei Gong2, , Lizhi Fan4, , Feifei Liu5, ,

  • 1 Lubin Environmental Protection Technology (Shanghai) Co., Ltd, Shanghai, China
  • 2 College of Life Science, Northeast Forestry University, Harbin, China
  • 3 Department of the Second General Surgery, Jixi Mine Hospital of Heilongjiang, Jixi, China
  • 4 Department of Geratology, The First Hospital of Harbin in Heilongjiang, Harbin, China
  • 5 Department of Medical Records, Hongqi Hospital Affiliated to Mudanjiang Medical College, Mudanjiang City, China
* Equal contribution

Received: February 5, 2019       Accepted: May 12, 2019       Published: May 28, 2019      

https://doi.org/10.18632/aging.101974
How to Cite

Copyright: Bai et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Statins, a class of hyperlipidemic drugs, are widely used cholesterol lowering drugs that selectively inhibit 3-hydroxy-3-methylglutaryl CoA reductase, which is the rate-limiting enzyme in cholesterol biosynthesis, leading to decreasing of cholesterol biosynthesis. Statins exert anti-tumoral effects on various cancer, including breast cancer. However, the molecular mechanisms for the actions were not fully elucidated. The purpose of this study was to elucidate the effects of statins on proliferation and apoptosis in the ER-negative breast cancer cell line MDA-MB-231. Our results showed that simvastatin increased the expression of miR-140-5p in a dose dependent manner via activating transcription factor NRF1, reduced cell proliferation and induced apoptosis, and we also found that SLC2A1 was a new target of miR-140-5p. In conclusion, data in this study shed light on the potential anti-tumoral effects of simvastatin in breast cancer and presents a highly promising therapeutic option, using drug and miRNA for combined treating cancers.

Abbreviations

NRF1: nuclear respiratory factor 1; miRNA: microRNA; SLC2A1: solute carrier family 2 member 1 (GLUT1); LAMC1: laminin subunit gamma 1; FGF9: fibroblast growth factor 9; p21: cyclin dependent kinase inhibitor 1A (CDKN1A); p27: cyclin dependent kinase inhibitor 1B (CDKN1B); NAC: N-Acetyl-L-cysteine.