Enhanced Efficacy of Histone Deacetylase Inhibitor Panobinostat Combined with Dual PI3K/mTOR Inhibitor BEZ235 Against Glioblastoma

Overview

Journal Nagoya J Med Sci

Specialty General Medicine

Date 2019 Apr 10

PMID 30962658

Citations 10

Authors

Wei Meng

Baocheng Wang

Weiwei Mao

Jiajia Wang

Yang Zhao

Qifeng Li

Chenran Zhang

Jie Ma

Affiliations

Soon will be listed here.

Abstract

Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Despite multiple treatment strategies, the prognosis is still poor. This study aimed to evaluate the efficacy of combination treatment of GBM with the histone deacetylase (HDAC) inhibitor panobinostat and dual phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor BEZ235. GBM cells were exposed to panobinostat and BEZ235 treatment alone or in combination, after which cell viability, proliferation and apoptosis were detected. Furthermore, the inhibitory mechanisms were investigated by Caspase-Glo assay, Western blot and qPCR analysis. We found that combination treatment with panobinostat and BEZ235 synergistically inhibited cell viability, markedly inhibited cell proliferation and induced apoptosis in GBM cells. Mechanistically, cotreatment with panobinostat and BEZ235 increased caspase 3/7 activity, suppressed proliferation- and antiapoptosis-related markers and AKT signaling in GBM cells. Cotreatment with panobinostat and BEZ235 warrants further evaluation in GBM therapy.

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