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Preclinical evaluation of the mTOR-PI3K inhibitor BEZ235 in nasopharyngeal cancer models.
- Source :
-
Cancer letters [Cancer Lett] 2014 Feb 01; Vol. 343 (1), pp. 24-32. Date of Electronic Publication: 2013 Sep 14. - Publication Year :
- 2014
-
Abstract
- The dual PI3K-mTOR inhibitor BEZ235 was evaluated in preclinical models of nasopharyngeal carcinoma (NPC). The IC50 value of BEZ235 for growth was in the nanomolar range in vitro, induce G1 cycle arrest and apoptosis, and inhibited AKT and mTOR signaling in most NPC cell lines. No synergistic effect was observed when BEZ235 was combined with chemotherapy. BEZ235 increased MAPK activation in vitro but not in vivo. A daily schedule was more effective than a weekly schedule on tumor growth and inhibition of downstream mTOR signaling in vivo. The activity of BEZ235 maybe independent of the PIK3CA amplification and mutation status.<br /> (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents pharmacology
Carcinoma
Cell Cycle
Cell Line, Tumor
Cell Survival
Cisplatin pharmacology
Enzyme Activation
Female
Humans
Inhibitory Concentration 50
MAP Kinase Signaling System
Mice
Mice, Nude
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms genetics
Neoplasm Transplantation
Paclitaxel pharmacology
Phosphoinositide-3 Kinase Inhibitors
TOR Serine-Threonine Kinases antagonists & inhibitors
Gene Expression Regulation, Neoplastic
Imidazoles pharmacology
Nasopharyngeal Neoplasms metabolism
Phosphatidylinositol 3-Kinases metabolism
Quinolines pharmacology
TOR Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7980
- Volume :
- 343
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cancer letters
- Publication Type :
- Academic Journal
- Accession number :
- 24041865
- Full Text :
- https://doi.org/10.1016/j.canlet.2013.09.007