title: Pharmacological inhibition of AKT sensitizes MCF-7 human breast cancer-initiating cells to radiation.
abstract: BACKGROUND
  Caner-initiating cells (CICs or cancer stem cells) have been shown both experimentally and clinically to be resistant to radiation. The mechanism underlying radioresistance remains unclear.
  
  
  METHODS
  In the present study, we screened 51 genes which are potentially important in mediating radioresistance of breast CICs.
  
  
  RESULTS
  The expression of AKT1 and AKT2 at protein and mRNA levels was dramatically increased among the screened genes by 8 Gy radiation treatment in MCF-7 mammosphere cells (predominantly CD24(-/low)/CD44(+) CICs), but not in the bulk population of MCF-7 cells (predominantly CD24(+)/CD44(+)). Using apoptosis and clonogenic survival assays, we found pharmacological inhibition of AKT with selective inhibitors of AKT sensitized MCF-7 mammosphere cells, but not MCF-7 monolayer cells to radiation.
  
  
  CONCLUSIONS
  The present findings suggest that treatment with AKT inhibitors prior to ionizing radiation treatment may be a potential benefit to patients with breast cancer, in particular to eradiate breast CICs.
authors.affiliation: Health Management Centre, Guangzhou First Municipal People's Hospital, Guangzhou Medical College, Guangzhou, Guangdong Province, China.
authors.forename: Jun-Fang
authors.initials: JF
authors.lastname: Zhan
authors.forename: Liang-Ping
authors.initials: LP
authors.lastname: Wu
authors.forename: Long-Hua
authors.initials: LH
authors.lastname: Chen
authors.forename: Ya-Wei
authors.initials: YW
authors.lastname: Yuan
authors.forename: Guo-Zhu
authors.initials: GZ
authors.lastname: Xie
authors.forename: Ai-Min
authors.initials: AM
authors.lastname: Sun
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhi-Xian
authors.initials: ZX
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology* / Q000528:radiation effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects* / Q000528:radiation effects*; D018874:Spheroids, Cellular / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects; D014965:X-Rays
chemical_list: D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt