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.