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

被引：27

作者：

Ma, Brigette B. Y. ^{[1
,2
]}

Lui, Vivian W. Y. ^{[3
]}

Hui, Connie W. C. ^{[1
,2
]}

Lau, Cecilia P. Y. ^{[1
,2
]}

Wong, Chi H. ^{[1
,2
]}

Hui, Edwin P. ^{[1
,2
]}

Ng, Margaret H. L. ^{[4
]}

Cheng, Suk H. ^{[4
]}

Tsao, Sai W. ^{[5
]}

Tsang, Chi-Man

Cheung, Crystal S. F. ^{[1
,2
]}

Ho, Kakiu ^{[1
,2
]}

Chan, Anthony T. C. ^{[1
,2
]}

机构：

[1] Chinese Univ Hong Kong, Hong Kong Canc Inst, State Key Lab Oncol South China,Canc Drug Testing, Sir YK Pao Ctr Canc,Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China

[2] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China

[3] Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15260 USA

[4] Chinese Univ Hong Kong, Dept Anat & Cellular Pathol, Hong Kong, Hong Kong, Peoples R China

[5] Univ Hong Kong, Dept Anat, Hong Kong, Hong Kong, Peoples R China

来源：

CANCER LETTERS | 2014年 / 343卷 / 01期

关键词：

Nasopharyngeal carcinoma; BEZ235; MAPK activation; PHOSPHATIDYLINOSITOL 3-KINASE/MAMMALIAN TARGET; COMPARATIVE GENOMIC HYBRIDIZATION; CARCINOMA-CELL LINES; RAPAMYCIN INHIBITOR; MAMMALIAN TARGET; LUNG-CANCER; PHARMACODYNAMIC SEPARATION; ANTITUMOR-ACTIVITY; PI3K INHIBITION; BREAST-CANCER;

D O I：

10.1016/j.canlet.2013.09.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 Ala 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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

引用

页码：24 / 32

页数：9

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