Ursolic acid enhances the therapeutic effects of oxaliplatin in colorectal cancer by inhibition of drug resistance

Cancer Sci. 2018 Jan;109(1):94-102. doi: 10.1111/cas.13425. Epub 2017 Nov 18.

Abstract

It has been reported that ursolic acid has anti-tumor activity and it enhances the therapeutic effect of oxaliplatin in colorectal cancer (CRC). However, the underlying mechanisms remain unknown. In the present study, the mechanisms of the enhancement of therapeutic effects through use of ursolic acid were investigated. We treated CRC cell lines HCT8 and SW480 with ursolic acid and oxaliplatin and monitored the effects on cell proliferation, apoptosis, reactive oxygen species (ROS) production and drug resistance gene production. We discovered that treatment with a combination of ursolic acid and oxaliplatin resulted in significant inhibition of cell proliferation, significantly increased apoptosis and ROS production, and significant inhibition of drug resistance gene expression. Our study provided evidence that ursolic acid enhances the therapeutic effects of oxaliplatin in colorectal cancer by ROS-mediated inhibition of drug resistance.

Keywords: colorectal cancer; drug resistance; proliferation; reactive oxygen species; ursolic acid.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Drug Resistance, Neoplasm / genetics
  • Drug Synergism
  • Humans
  • Mice
  • Organoplatinum Compounds / administration & dosage*
  • Organoplatinum Compounds / pharmacology
  • Oxaliplatin
  • Reactive Oxygen Species / metabolism*
  • Treatment Outcome
  • Triterpenes / administration & dosage*
  • Triterpenes / pharmacology
  • Xenograft Model Antitumor Assays

Substances

  • Organoplatinum Compounds
  • Reactive Oxygen Species
  • Triterpenes
  • Oxaliplatin
  • ursolic acid