Ezetimibe inhibits the migration and invasion of triple-negative breast cancer cells by targeting TGFβ2 and EMT

FEBS Open Bio. 2024 May;14(5):831-842. doi: 10.1002/2211-5463.13797. Epub 2024 Mar 26.

Abstract

The important role of cholesterol in tumor metastasis has been widely studied in recent years. Ezetimibe is currently the only selective cholesterol uptake inhibitor on the market. Here, we explored the effect of ezetimibe on breast cancer metastasis by studying its impact on breast cancer cell migration, invasion, and epithelial-mesenchymal transition (EMT). Differential gene expression analysis and validation were also carried out to compare ezetimibe-treated and untreated breast cancer cells. Finally, breast cancer cells overexpressing TGFβ2 were constructed, and the effect of TGFβ2 on the migration and invasion of ezetimibe-treated breast cancer cells was examined. Our results show that ezetimibe treatment of breast cancer cells inhibited cell migration, invasion, and EMT, and it significantly suppressed the expression of TGFβ2. Overexpression of TGFβ2 reversed the inhibitory effect of ezetimibe on the migration and invasion of breast cancer cells. Taken together, our results suggest that ezetimibe might be a potential candidate for the treatment of breast cancer metastasis.

Keywords: TGFβ2; breast cancer; cholesterol; ezetimibe; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement* / drug effects
  • Epithelial-Mesenchymal Transition* / drug effects
  • Ezetimibe* / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Neoplasm Invasiveness
  • Transforming Growth Factor beta2* / metabolism
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / metabolism
  • Triple Negative Breast Neoplasms* / pathology

Substances

  • Ezetimibe
  • Transforming Growth Factor beta2
  • TGFB2 protein, human