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Preclinical evaluation of the mTOR-PI3K inhibitor BEZ235 in nasopharyngeal cancer models.

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.
AuthorsBrigette B Y Ma, Vivian W Y Lui, Connie W C Hui, Cecilia P Y Lau, Chi H Wong, Edwin P Hui, Margaret H L Ng, Suk H Cheng, Sai W Tsao, Chi-Man Tsang, Crystal S F Cheung, Kakiu Ho, Anthony T C Chan
JournalCancer letters (Cancer Lett) Vol. 343 Issue 1 Pg. 24-32 (Feb 01 2014) ISSN: 1872-7980 [Electronic] Ireland
PMID24041865 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Imidazoles
  • Phosphoinositide-3 Kinase Inhibitors
  • Quinolines
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Paclitaxel
  • Cisplatin
  • dactolisib
Topics
  • Animals
  • Antineoplastic Agents (pharmacology)
  • Carcinoma
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Survival
  • Cisplatin (pharmacology)
  • Enzyme Activation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Imidazoles (pharmacology)
  • Inhibitory Concentration 50
  • MAP Kinase Signaling System
  • Mice
  • Mice, Nude
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms (genetics, metabolism)
  • Neoplasm Transplantation
  • Paclitaxel (pharmacology)
  • Phosphatidylinositol 3-Kinases (metabolism)
  • Phosphoinositide-3 Kinase Inhibitors
  • Quinolines (pharmacology)
  • TOR Serine-Threonine Kinases (antagonists & inhibitors, metabolism)

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