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

Brigette 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

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)24-32
Number of pages9
JournalCancer Letters
Volume343
Issue number1
DOIs
StatePublished - Feb 1 2014
Externally publishedYes

Keywords

  • BEZ235
  • MAPK activation
  • Nasopharyngeal carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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