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

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.
AuthorsMeng-meng Lv, Xing-ya Zhu, Wei-xian Chen, Shan-liang Zhong, Qing Hu, Teng-fei Ma, Jun Zhang, Lin Chen, Jin-hai Tang, Jian-hua Zhao
JournalTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 35 Issue 11 Pg. 10773-9 (Nov 2014) ISSN: 1423-0380 [Electronic] Netherlands
PMID25077924 (Publication Type: Journal Article)
Chemical References
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Taxoids
  • Docetaxel
Topics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
  • Apoptosis (drug effects)
  • Blotting, Western
  • Breast Neoplasms (drug therapy, metabolism, pathology)
  • Cell Proliferation (drug effects)
  • Docetaxel
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Exosomes
  • Female
  • Flow Cytometry
  • Humans
  • Taxoids (pharmacology)
  • Tumor Cells, Cultured

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