Co-treatment of Salinomycin Sensitizes AZD5363-treated Cancer Cells Through Increased Apoptosis

Anticancer Res. 2015 Sep;35(9):4741-7.

Abstract

AZD5363, an inhibitor of protein kinase B (AKT), is currently in clinical trials assessing the potential of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. The purpose of the present study was to identify conditions that increase the sensitivity of cancer cells to AZD5363. Microscopic examination revealed that treatment of cancer cells with a low concentration of salinomycin reduced cellular growth of AZD5363-treated breast cancer cells. Furthermore, fluorescence-activated cell sorting (FACS) analysis, Hoechst staining, and annexin V staining revealed that co-treatment with salinomycin sensitizes AZD5363-treated cancer cells via increased apoptosis with S-phase arrest. These results suggest that salinomycin can be applied to increase treatment efficacy for AZD5363-treated cancer cells. Our findings may contribute to improving the efficacy of the development of AZD5363-based sensitization therapies for patients with cancer.

Keywords: AZD5363; apoptosis; cancer; salinomycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis* / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor*
  • Female
  • Humans
  • Pyrans / pharmacology
  • Pyrans / therapeutic use*
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use*
  • Pyrroles / pharmacology
  • Pyrroles / therapeutic use*
  • S Phase

Substances

  • Pyrans
  • Pyrimidines
  • Pyrroles
  • salinomycin
  • capivasertib