title: Bioluminescence Imaging to Monitor the Effects of the Hsp90 Inhibitor NVP-AUY922 on NF-κB Pathway in Endometrial Cancer.
abstract: In this study, we first aimed to evaluate the effects in vitro and in vivo, of the Hsp90 inhibitor NVP-AUY922, in endometrial cancer (EC). We also aimed to track nuclear factor kappa B (NF-κB) signalling, a key pathway involved in endometrial carcinogenesis and to check whether NVP-AUY922 treatment modulates it both in vitro and in vivo.
  
  
  
  I n vitro effects of NVP-AUY922 on EC cell growth and the signalling pathways were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), clonogenic assays, Western Blot and luciferase assay. NVP-AUY922 effect on Ishikawa (IK) xenograft growth was evaluated in vivo, and NF-κB activity was monitored using bioluminescence imaging.
  
  
  
  NVP-AUY922 inhibited the growth of three endometrial cell lines tested in vitro. In vivo, NVP-AUY922 reduced tumour growth of 47 % (p = 0.042) compared to control condition. Moreover, the bioluminescence signal of the tumours harbouring IK NF-κB-LUC cells was significantly reduced in NVP-AUY922-treated animals compared to untreated ones.
  
  
  
  NVP-AUY922 reduced EC tumour growth and NF-κB signalling both in vitro and in vivo. As therapeutic resistance of EC remains a challenge for oncologists nowadays, we think that NVP-AUY922 represents a valid alternative to conventional chemotherapy, and we believe that this approach for assessing and tracking the activation of NF-κB pathway may be of therapeutic benefit.
authors.affiliation: Department of Pathology and Molecular Genetics HUAV, Dept de Ciències Mèdiques Bàsiques, Institut de Recerca Biomedica de Lleida, Univeristy of Lleida, IRBLleida, Avenida Rovira Roure, No. 80, 25198, Lleida, Spain. andreeyeramian@cmb.udl.es.
authors.forename: Andree
authors.initials: A
authors.lastname: Yeramian
authors.affiliation: Department of Radiation Oncology, Hospital Universitari Arnau de Vilanova, Avenida Rovira Roure, No. 80, 25198, Lleida, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: García
authors.affiliation: Department of Pathology and Molecular Genetics HUAV, Dept de Ciències Mèdiques Bàsiques, Institut de Recerca Biomedica de Lleida, Univeristy of Lleida, IRBLleida, Avenida Rovira Roure, No. 80, 25198, Lleida, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Bergadà
authors.affiliation: Department of Pathology and Molecular Genetics HUAV, Dept de Ciències Mèdiques Bàsiques, Institut de Recerca Biomedica de Lleida, Univeristy of Lleida, IRBLleida, Avenida Rovira Roure, No. 80, 25198, Lleida, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Domingo
authors.affiliation: Department of Pathology and Molecular Genetics HUAV, Dept de Ciències Mèdiques Bàsiques, Institut de Recerca Biomedica de Lleida, Univeristy of Lleida, IRBLleida, Avenida Rovira Roure, No. 80, 25198, Lleida, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Santacana
authors.affiliation: Biostatistics Unit, Hospital Universitari Arnau de Vilanova, University of Lleida, IRB-Lleida, Avenida Rovira Roure, No. 80, 25198, Lleida, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Valls
authors.affiliation: Biostatistics Unit, Hospital Universitari Arnau de Vilanova, University of Lleida, IRB-Lleida, Avenida Rovira Roure, No. 80, 25198, Lleida, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Martinez-Alonso
authors.affiliation: Department of Radiation Oncology, Hospital Universitari Arnau de Vilanova, Avenida Rovira Roure, No. 80, 25198, Lleida, Spain.
authors.forename: José-Antonio
authors.initials: JA
authors.lastname: Carceller
authors.affiliation: Department of Oncology, Hospital Universitari Arnau de Vilanova, University of Lleida, IRB-Lleida, Avenida Rovira Roure, No. 80, 25198, Lleida, Spain.
authors.forename: Antonio Llombart
authors.initials: AL
authors.lastname: Cussac
authors.affiliation: Department of Pathology and Molecular Genetics HUAV, Dept de Ciències Mèdiques Bàsiques, Institut de Recerca Biomedica de Lleida, Univeristy of Lleida, IRBLleida, Avenida Rovira Roure, No. 80, 25198, Lleida, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Dolcet
authors.affiliation: Department of Pathology and Molecular Genetics HUAV, Dept de Ciències Mèdiques Bàsiques, Institut de Recerca Biomedica de Lleida, Univeristy of Lleida, IRBLleida, Avenida Rovira Roure, No. 80, 25198, Lleida, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Matias-Guiu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D003952:Diagnostic Imaging / Q000379:methods*; D016889:Endometrial Neoplasms / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D008156:Luciferases / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D012118:Resorcinols / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: C528044:5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D007555:Isoxazoles; D016328:NF-kappa B; D012118:Resorcinols; D008156:Luciferases
keywords: Bioluminescence; Endometrial carcinoma; Hsp90; NF-κB; Survival pathways