title: Hsp90 inhibition by NVP-AUY922 and NVP-BEP800 decreases migration and invasion of irradiated normoxic and hypoxic tumor cell lines.
abstract: This study explores the impact of Hsp90 inhibitors NVP-AUY922 and NVP-BEP800 in combination with ionizing radiation (IR) on the migration and invasion of lung carcinoma A549 and glioblastoma SNB19 cells, under normoxia or hypoxia. Independent of oxygen concentration, both drugs decreased the migration and invasion rates of non-irradiated tumor cells. Combined drug-IR treatment under hypoxia inhibited cell invasion to a greater extent than did each treatment alone. Decreased migration of cells correlated with altered expression of several matrix-associated proteins (FAK/p-FAK, Erk2, RhoA) and impaired F-actin modulation. The anti-metastatic efficacy of the Hsp90 inhibitors could be useful in combinational therapies of cancer.
authors: Department of Radiation Oncology, University of Würzburg, Josef-Schneider-Strasse 11, D-97080 Würzburg, Germany.
authors: Susanne
authors: S
authors: Hartmann
authors: Nadine
authors: N
authors: Günther
authors: Marlene
authors: M
authors: Biehl
authors: Astrid
authors: A
authors: Katzer
authors: Sebastian
authors: S
authors: Kuger
authors: Eike
authors: E
authors: Worschech
authors: Vladimir L
authors: VL
authors: Sukhorukov
authors: Georg
authors: G
authors: Krohne
authors: Heiko
authors: H
authors: Zimmermann
authors: Michael
authors: M
authors: Flentje
authors: Cholpon S
authors: CS
authors: Djuzenova
mesh_terms: D015153:Blotting, Western; D001932:Brain Neoplasms / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D005434:Flow Cytometry; D005909:Glioblastoma / Q000473:pathology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology; D008855:Microscopy, Electron, Scanning; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D011743:Pyrimidines / Q000494:pharmacology*; D012118:Resorcinols / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: C528044:5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide; D018841:HSP90 Heat-Shock Proteins; D007555:Isoxazoles; C547235:NVP-BEP800; D011743:Pyrimidines; D012118:Resorcinols