The Effects of Eribulin on Breast Cancer Microenvironment Identified Using Eribulin-resistant Breast Cancer Cell Lines

Anticancer Res. 2019 Aug;39(8):4031-4041. doi: 10.21873/anticanres.13559.

Abstract

Background/aim: Eribulin is currently used to treat advanced and metastatic breast cancer in the clinical setting; however, its efficacy is inhibited by resistance acquisition in many cases. Thus, the present study established two eribulin-resistant breast-cancer cell lines, and used these to investigate the mechanisms that underly eribulin-resistance acquisition.

Materials and methods: Eribulin-resistant breast-cancer cell lines were generated by culturing MDA-MB-231 and MCF-7 cells with increasing concentrations of eribulin.

Results: The eribulin-resistant cells acquired resistance to eribulin, as well as several other anticancer drugs. After eribulin treatment, the eribulin-resistant cell lines showed no morphological change, no increased expression of epithelial-cadherin, nor any significant alteration in cell-cycle distribution. In contrast, the expression levels of programmed death-ligand 1 were increased in the MCF-7/eribulin-resistant compared to MCF-7 cells.

Conclusion: The herein developed eribulin-resistant cell lines acquired cross-resistance to various anticancer agents, and displayed resistance to eribulin-induced effects on microtubule function and epithelial-mesenchymal transition (EMT).

Keywords: Eribulin; breast cancer; epithelial-mesenchymal transition; microenvironment; resistance.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Breast / drug effects
  • Breast / pathology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Drug Resistance, Neoplasm / genetics*
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Furans / administration & dosage*
  • Furans / adverse effects
  • Humans
  • Ketones / administration & dosage*
  • Ketones / adverse effects
  • MCF-7 Cells
  • Mice
  • Tumor Microenvironment / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Furans
  • Ketones
  • eribulin