Targeting renal cell carcinoma with NVP-BEZ235, a dual PI3K/mTOR inhibitor, in combination with sorafenib.

Détails

Ressource 1Télécharger: BIB_407039255E66.P001.pdf (704.30 [Ko])
Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_407039255E66
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Targeting renal cell carcinoma with NVP-BEZ235, a dual PI3K/mTOR inhibitor, in combination with sorafenib.
Périodique
Molecular Cancer
Auteur(s)
Roulin D., Waselle L., Dormond-Meuwly A., Dufour M., Demartines N., Dormond O.
ISSN
1476-4598 (Electronic)
ISSN-L
1476-4598
Statut éditorial
Publié
Date de publication
2011
Volume
10
Pages
-
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: epublish
Résumé
Background: Targeted therapies for metastatic renal cell carcinoma (RCC), including mammalian target of rapamycin (mTOR) inhibitors and small-molecule multikinase inhibitors, have produced clinical effects. However, most patients acquire resistance over time. Thus, new therapeutic strategies need to be developed. Here, we evaluated the effect of the dual PI3K/mTOR inhibitor NVP-BEZ235, in combination with the multikinase inhibitor sorafenib on renal cancer cell proliferation and survival in vitro as well as on tumor growth in vivo.Methods: The renal carcinoma cell lines 786-0 and Caki-1 were treated with NVP-BEZ235 or sorafenib, either alone or in combination. Tumor cell proliferation and apoptosis were investigated in vitro. The anticancer efficacy of NVP-BEZ235 alone, or in combination with sorafenib, was also evaluated on RCC xenografts in nude mice.Results: Treatment of 786-0 and Caki-1 cells with NVP-BEZ235 or sorafenib resulted in reduced tumor cell proliferation and increased tumor cell apoptosis in vitro. The combination of NVP-BEZ235 and sorafenib was more effective than each compound alone. Similarly, in vivo, NVP-BEZ235 or sorafenib reduced the growth of xenografts generated from 786-0 or Caki-1 cells. The antitumor efficacy of NVP-BEZ235 in combination with sorafenib was superior to NVP-BEZ235 or sorafenib alone.Conclusions: Our findings indicate that the simultaneous use of NVP-BEZ235 and sorafenib has greater antitumor benefit compared to either drug alone and thus provides a treatment strategy in RCC.
Pubmed
Web of science
Open Access
Oui
Création de la notice
09/09/2011 10:32
Dernière modification de la notice
08/05/2019 17:37
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