title: Experimental study on the regulation of erlotinib-induced radiosensitization with an anti-c-MET monoclonal antibody.
abstract: OBJECTIVE
  Erlotinib is a novel therapeutic agent for cancer treatment. This study was performed to investigate the role of c-MET-PI3K-AKT pathway in the regulation of erlotinib-induced radiosensitization.
  
  
  METHODS
  A973 lung adenocarcinoma cells treated with 6 Gy of radiation were incubated in the presence of erlotinib. The apoptotic rate after 24 hours, the colony-formating rate after 14 days, and changes in the c-MET expression levels after 14 days of irradiation were examined. Surviving fractions in different treatment groups (blank control, radiation alone, erlotinib alone, anti-c-MET monoclonal antibody alone, combined erlotinib and radiation, and combined erlotinib and radiation with anti-c-MET monoclonal antibody groups) were determined, the survival curves were plotted, and the sensitizer enhancement ratio was calculated using colony formation assays. Expressions of c-MET, p-c-MET, PI3K, AKT, and p-AKT in cells in different treatment groups were examined by Western blot analysis.
  
  
  RESULTS
  The apoptotic rate in the combined erlotinib and radiation group was higher than those in single treatment groups; however, the colony-forming rate remained approximately 2.04 ± 1.02%. The expression of c-MET in colony-forming cells in the combined group significantly increased, and the blockade of c-MET activity significantly enhanced the radiosensitizing effect of erlotinib. The expression of c-Met, p-c-MET, PI3K, AKT, and p-AKT among colony-forming cells significantly decreased upon the inhibition of c-MET.
  
  
  CONCLUSIONS
  Upregulated activity of the c-MET-PI3K-AKT pathway was found to be important for cell survival under combined the treatment with erlotinib and radiation. The blockade of the c-MET-PI3K-AKT signaling pathway enhanced the radiosensitizing effect of erlotinib.
authors.affiliation: Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin Lung Cancer Center, Tianjin, China.
authors.forename: Hong-Qing
authors.initials: HQ
authors.lastname: Zhuang
authors.affiliation: Department of Hematology, Weifang People's Hospital, Weifang, Shandong province China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: Department of Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong province China.
authors.forename: Qifu
authors.initials: Q
authors.lastname: Bo
authors.affiliation: Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin Lung Cancer Center, Tianjin, China.
authors.forename: Yihang
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin Lung Cancer Center, Tianjin, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin Lung Cancer Center, Tianjin, China.
authors.forename: Lu-Jun
authors.initials: LJ
authors.lastname: Zhao
authors.affiliation: Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin Lung Cancer Center, Tianjin, China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yuan
authors.affiliation: Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin Lung Cancer Center, Tianjin, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
keywords: Acquired drug resistance; PI3K pathway; Radiation resistance; Radiosensitization; Tyrosine kinase inhibitor