title: Selective inhibition of survival signal transduction pathways enhanced radiosensitivity in human esophageal cancer cell lines in vitro.
abstract: OBJECTIVE
  The purpose of this study was to examine how selective inhibition of the survival signal transduction pathways affects radiosensitivity in human cancer cell lines.
  
  
  METHODS
  Two human esophageal cancer cell lines, TE-1 (mutant p53) and TE2 (wild-type p53), were used. To inhibit the pathways selectively, 3 specific kinase inhibitors, AG1478 (an inhibitor of EGFR), PD98059 (an inhibitor of MEK) and LY294002 (an inhibitor of PI3K), were combined with radiation.
  
  
  RESULTS
  Radiation in combination with these kinase inhibitors potentiated radiation-induced cell killing synergistically. Enhancement ratios were greater in TE-2 than those in TE-1. Radiation in combination with kinase inhibitors increased the expression of the active form of caspase-3 and the PARP cleavage only in TE-2 that has wild-type p53.
  
  
  CONCLUSIONS
  Targeting the key molecules of the survival signal transduction pathway resulted in potentiation of radiation-induced cell killing. The results of this study suggest that the survival signal transduction pathways would be a molecular target in enhancing radiosensitivity.
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan. takimoto@showa.gunma-u.ac.jp
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Akimoto
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nonaka
authors.forename: Koichi
authors.initials: K
authors.lastname: Harashima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Norio
authors.initials: N
authors.lastname: Mitsuhashi
mesh_terms: D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D003131:Combined Modality Therapy; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000201:enzymology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors; D009025:Morpholines / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D011836:Radiation Tolerance / Q000187:drug effects* / Q000502:physiology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D011859:Radiography; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D061945:Caspase Inhibitors; D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D011838:Radiation-Sensitizing Agents; D020032:Tyrphostins; C101044:RTKI cpd; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D011065:Poly(ADP-ribose) Polymerases; D048728:MAP Kinase Kinase Kinase 1; D020930:MAP Kinase Kinase Kinases; C482576:MAP3K1 protein, human; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one