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

Autor:	S. H. Cheng, Brigette B.Y. Ma, Crystal S.F. Cheung, Cecilia P.Y. Lau, Connie W.C. Hui, Chi Man Tsang, Margaret H.L. Ng, Vivian Wai Yan Lui, Anthony T.C. Chan, Sai W. Tsao, Kakiu Ho, C.H. Wong, Edwin P. Hui
Rok vydání:	2013
Předmět:	Cancer Research medicine.medical_specialty Paclitaxel Cell Survival MAP Kinase Signaling System medicine.medical_treatment Mice Nude Antineoplastic Agents Biology Inhibitory Concentration 50 Mice Phosphatidylinositol 3-Kinases In vivo Internal medicine Cell Line Tumor medicine Animals Humans Protein kinase B PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors Chemotherapy Nasopharyngeal Carcinoma TOR Serine-Threonine Kinases Carcinoma Cell Cycle Imidazoles Nasopharyngeal Neoplasms medicine.disease In vitro Enzyme Activation Gene Expression Regulation Neoplastic Endocrinology Oncology Nasopharyngeal carcinoma Cell culture Apoptosis Cancer research Quinolines Female Cisplatin Neoplasm Transplantation
Zdroj:	Cancer letters. 343(1)
ISSN:	1872-7980
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d6dcea542db000151cc7edf7ed14db41 https://pubmed.ncbi.nlm.nih.gov/24041865 Zobrazit plný text záznamu Full Text from ScienceDirect