期刊
MOLECULAR IMAGING AND BIOLOGY
卷 18, 期 4, 页码 545-556出版社
SPRINGER
DOI: 10.1007/s11307-015-0907-8
关键词
Endometrial carcinoma; Hsp90; NF-kappa B; Survival pathways; Bioluminescence
资金
- Grupos estables AECC [AECC-2011]
- AECC
- [PI10/00922]
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-kappa B) 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-kappa B 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-kappa B-LUC cells was significantly reduced in NVP-AUY922-treated animals compared to untreated ones. NVP-AUY922 reduced EC tumour growth and NF-kappa B 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-kappa B pathway may be of therapeutic benefit.
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