Autophagy contributes to the enrichment and survival of colorectal cancer stem cells under oxaliplatin treatment

Cancer Lett. 2015 May 28;361(1):128-36. doi: 10.1016/j.canlet.2015.02.045. Epub 2015 Mar 5.

Abstract

Currently, chemoresistance is an important cause of treatment failure in colorectal cancer. Cancer stem cells, which are a population of multi-potent cells with the capacity to self-renew and differentiate, have been found to participate in chemoresistance. In the present study, the chemotherapeutic drug oxaliplatin induced autophagy in colorectal cancer cell lines, which in turn protected cancer cells from apoptosis. Further results showed that oxaliplatin-induced autophagy enriched the population of colorectal CSCs and participated in maintaining the stemness of colorectal CSCs, thus making the cells more resistant to chemotherapy. Taken together, the results indicate that autophagy might enhance the chemoresistance of colorectal cancer cells by protecting the stemness and chemoresistance of colorectal CSCs. Our study demonstrates that autophagy plays a pro-survival role in colorectal CSCs subjected to oxaliplatin. Therefore, targeting autophagy may be considered as a potential therapeutic strategy to address chemoresistance in the treatment of colorectal cancer.

Keywords: Autophagy; Cancer stem cells; Chemoresistance; Colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Autophagy / drug effects*
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Drug Resistance, Neoplasm / drug effects
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology*
  • Organoplatinum Compounds / pharmacology*
  • Oxaliplatin
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Organoplatinum Compounds
  • RNA, Messenger
  • Oxaliplatin