title: Interaction of radiation and gefitinib on a human lung cancer cell line with mutant EGFR gene in vitro.
abstract: OBJECTIVE
  To investigate the effect of gefitinib in combination with irradiation using HCC827 cells, a human lung cancer cell line bearing epidermal growth factor receptor (EGFR) mutation.
  
  
  METHODS
  The effects of treatment with radiation with and without gefitinib on HCC827 cells were assessed using a clonogenic assay. Apoptosis was measured by flow cytometry and EGFR signal transduction was evaluated by western blotting.
  
  
  RESULTS
  The Dq - quasi-threshold dose, the dose at which the straight portion of the survival curve, extrapolated backward, cuts the dose axis drawn through a survival fraction of unity - after radiation-alone and after combination treatment were 0.41±0.09 Gy and 0.08±0.11 Gy, respectively; thus indicating that combination treatment resulted in supra-additive effects of radiation. There was no significant difference on the D0 - final slope of the survival curve (the dose required to reduce the fraction of surviving cells to 37% of its previous value) - between-radiation alone and the combination treatment. Apoptosis significantly increased after the combination treatment in comparison to what was observed after radiation-alone. The expression of phosphorylated EGFR (pEGFR), phosphorylated ERK1/2 (pERK1/2) and phosphorylated AKT (pAKT) after the combination decreased in comparison to what was observed after radiation-alone.
  
  
  CONCLUSIONS
  Gefitinib enhances radiosensitivity of supra-additively HCC827 cells by inhibiting the activation of the anti-apoptotic and proliferative signal transduction pathways.
authors.affiliation: Department of Radiation Oncology, Gunma University, Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan. sato-y@gunma-u.ac.jp
authors.forename: Yumi
authors.initials: Y
authors.lastname: Sato
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ebara
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sunaga
authors.forename: Takeo
authors.initials: T
authors.lastname: Takahashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D059248:Chemoradiotherapy; D005434:Flow Cytometry; D000077156:Gefitinib; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D009154:Mutation; D011799:Quinazolines / Q000008:administration & dosage*; D011836:Radiation Tolerance / Q000187:drug effects* / Q000235:genetics; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects
chemical_list: D011799:Quinazolines; D011838:Radiation-Sensitizing Agents; D000077156:Gefitinib