Autophagy protects breast cancer cells from epirubicin-induced apoptosis and facilitates epirubicin-resistance development

Autophagy. 2011 Sep;7(9):1035-44. doi: 10.4161/auto.7.9.16521. Epub 2011 Sep 1.


Epirubicin (EPI) is one of the most effective drugs against cancer. But the acquired resistance of cancer cells to EPI is becoming a major obstacle for successful cancer therapy. Recently, some studies have revealed that macroautophagy (here referred to as autophagy) may protect the cancer cell from anticancer drug-induced death, so autophagy might be related to the development of drug resistance to these reagents. However, the relationship between autophagy and drug resistance has yet to be defined. Our study showed that EPI induced autophagy in human breast cancer MCF-7 cells. And the EPI-induced autophagy protected MCF-7 cells from EPI-induced apoptosis. Furthermore, autophagy was elevated in EPI-resistant MCF-7 cells (MCF-7er cells), and inhibition of autophagy restored the sensitivity of MCF-7er cells to EPI. Therefore, autophagy is a prosurvival factor and has a role in the development of EPI-acquired resistance in EPI-treated MCF-7 cells. Also, this finding indicates that the use of clinically applicable autophagy inhibitors might be one of the important strategies for breast cancer therapy.

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / drug effects*
  • Autophagy-Related Protein 7
  • Beclin-1
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology*
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cytoprotection / drug effects*
  • Drug Resistance, Neoplasm / drug effects*
  • Epirubicin / pharmacology*
  • Female
  • Humans
  • Macrolides / pharmacology
  • Membrane Proteins / metabolism
  • RNA, Small Interfering / metabolism
  • Ubiquitin-Activating Enzymes / metabolism


  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Macrolides
  • Membrane Proteins
  • RNA, Small Interfering
  • Epirubicin
  • bafilomycin A1
  • Caspases
  • ATG7 protein, human
  • Autophagy-Related Protein 7
  • Ubiquitin-Activating Enzymes