Exosomes mediate drug resistance transfer in MCF-7 breast cancer cells and a probable mechanism is delivery of P-glycoprotein

Tumour Biol. 2014 Nov;35(11):10773-9. doi: 10.1007/s13277-014-2377-z. Epub 2014 Jul 31.

Abstract

Acquired drug resistance is a major obstacle to chemotherapy of cancers. In this study, we aim to investigate the role of exosomes in drug-resistance transfer between breast cancer cells and detect the probable mechanism. A docetaxel-resistant variant of MCF-7 cell line (MCF-7/DOC) was established and then compared with the drug-sensitive variant (MCF-7/S). Exosomes were expelled from the cell supernatant using ultracentrifugation. Drug resistance was assessed by apoptosis assay and MTT examination. Expressions of P-glycoprotein (P-gp) were analyzed by flow cytometry. Stained exosomes were absorbed by receipt cells. MCF-7/S in the presence of exosomes extracted from the supernatant of MCF-7/DOC (DOC/exo) acquired drug resistance, while MCF-7/S exposed to their own exosomes (S/exo) did not. P-gp expression patterns of exosomes were similar as the originated cells. P-gp expression of MCF-7/S increased after incubation with DOC/exo and was affected by the amount of exosomes. Exosomes are effective in transferring drug resistance as well as P-gp from drug-resistant breast cancer cells to sensitive ones. The delivery of P-gp via exosomes may be a mechanism of exosome-mediated drug resistance transfer.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Apoptosis / drug effects
  • Blotting, Western
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Docetaxel
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Exosomes*
  • Female
  • Flow Cytometry
  • Humans
  • Taxoids / pharmacology*
  • Tumor Cells, Cultured

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Taxoids
  • Docetaxel