Andree Yeramian1, Virginia García2, Laura Bergadà3, Mónica Domingo3, Maria Santacana3, Joan Valls4, Montserrat Martinez-Alonso4, José-Antonio Carceller2, Antonio Llombart Cussac5, Xavier Dolcet3, Xavier Matias-Guiu3. 1. 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. 2. Department of Radiation Oncology, Hospital Universitari Arnau de Vilanova, Avenida Rovira Roure, No. 80, 25198, Lleida, Spain. 3. 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. 4. Biostatistics Unit, Hospital Universitari Arnau de Vilanova, University of Lleida, IRB-Lleida, Avenida Rovira Roure, No. 80, 25198, Lleida, Spain. 5. Department of Oncology, Hospital Universitari Arnau de Vilanova, University of Lleida, IRB-Lleida, Avenida Rovira Roure, No. 80, 25198, Lleida, Spain.
Abstract
PURPOSE: 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. PROCEDURES: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: 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. PROCEDURES: 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. RESULTS: 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. CONCLUSIONS: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.
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