title: In vitro combined modality treatment of prostate carcinoma cells with 17-(allylamino)-17-demethoxygeldanamycin and ionizing radiation.
abstract: BACKGROUND
  The effect of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), a benzoquinone-ansamycin-type Hsp90-inhibitor, on the expression of focal adhesion kinase (FAK) and, when combined with ionizing radiation, on the clonogenicity of prostate cancer cells were determined.
  
  
  METHODS
  FAK was analyzed by Western immunoblot. Prostate carcinoma cells were exposed either to 17-AAG alone or combined with a single radiation fraction of 3 Gy.
  
  
  RESULTS
  FAK concentrations were reduced by 17-AAG in a time-dependent manner. Treatment with 100 nM 17-AAG for 24 h reduced clonogenicity by 90%. The plot of surviving fraction versus radiation energy dose yielded roughly parallel graphs for solvent- and 17-AAG-treated cells.
  
  
  CONCLUSIONS
  17-AAG induced rapid degradation of FAK A single radiation fraction of 3 Gy did not enhance the dose-dependent drug-effect on survival. In this sequence, the combined effect of both modalities towards clonogenicity was largely additive.
authors.affiliation: Clinic for Radiation Therapy, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany. hans-joachim.ochel@medizin.uni-magdeburg.de
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Ochel
authors.forename: Günther
authors.initials: G
authors.lastname: Gademann
mesh_terms: D016227:Benzoquinones; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D047029:Lactams, Macrocyclic; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000532:radiotherapy*; D017828:Rifabutin / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D017828:Rifabutin; C112765:tanespimycin; D051416:Focal Adhesion Protein-Tyrosine Kinases