title: The different radiosensitivity when combining erlotinib with radiation at different administration schedules might be related to activity variations in c-MET-PI3K-AKT signal transduction.
abstract: OBJECTIVE
  The aim of this paper was to investigate the efficacy and activity variation associated with phosphoinositide 3-kinase (PI3K) signal transduction when combining erlotinib with radiation, using different administration schedules.
  
  
  METHODS
  Erlotinib was delivered to A973 cancer cells in the following three ways: (1) irradiation after administration, (2) irradiation upon administration, and, (3) irradiation before administration. The cell-survival rates were detected using colony-forming assays, while cell apoptosis was detected with flow cytometry. The expression levels of C-MET, p-C-MET, AKT, and p-AKT were determined via Western blotting analysis, under 6 Gy irradiation with/ without erlotinib.
  
  
  RESULTS
  The sensitizer enhancement ratios (SERs) of erlotinib irradiation after administration, irradiation upon administration, and irradiation before administration groups were 2.19, 1.53, and 1.38, respectively. A higher apoptosis rate was observed when irradiation was delivered after erlotinib. In addition, changes in cell apoptosis were found to be related to concurrent changes in C-MET, p-C-MET, AKT, and p-AKT expression. Protein expression increased in the combination groups, with trends showing a negative relationship with cell apoptosis.
  
  
  CONCLUSIONS
  The radiosensitive effect of erlotinib varied because of the different administration schedules; this variation may be related to PI3K signal transduction and its associated regulating effect.
authors.affiliation: Department of Radiotherapy, Tianjin Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, and Tianjin Lung Cancer Center, Tianjin, People's Republic of China.
authors.forename: Hong-Qing
authors.initials: HQ
authors.lastname: Zhuang
authors.forename: Qi-Fu
authors.initials: QF
authors.lastname: Bo
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yuan
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Lu-Jun
authors.initials: LJ
authors.lastname: Zhao
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
keywords: PI3K; erlotinb; radiosensitization effects; tyrosine kinase inhibitor