Metformin inhibits tumor cell migration via down-regulation of MMP9 in tamoxifen-resistant breast cancer cells

Anticancer Res. 2014 Aug;34(8):4127-34.

Abstract

Metformin is the most widely used anti-diabetic drug in the world. Recent evidence indicates that metformin could potentially inhibit tumorigenesis. In the present study, we found that metformin inhibited cell migration and invasion of phorbol 12-myristate 13-acetate-induced MCF-7 and tamoxifen-resistant MCF-7 breast cancer cells. This inhibition was correlated with the modulation of matrix metalloproteinase-9 (MMP9) via the suppression of its expression and proteolytic activity. These results indicate that metformin leads to the suppression of migration and invasion through regulation of MMP9 and it may have potential as an anticancer drug for therapy in human breast cancer, especially of chemoresistant cancer cells.

Keywords: MMP9; Metformin; invasion; migration; tamoxifen resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Movement / drug effects*
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • MCF-7 Cells
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Metformin / pharmacology*
  • Neoplasm Invasiveness
  • Promoter Regions, Genetic
  • Tamoxifen / pharmacology*

Substances

  • Tamoxifen
  • Metformin
  • MMP9 protein, human
  • Matrix Metalloproteinase 9