Metformin and temozolomide act synergistically to inhibit growth of glioma cells and glioma stem cells in vitro and in vivo
Abstract
// Zhiyun Yu 1 , Gang Zhao 1 , Guifang Xie 2 , Liyan Zhao 3 , Yong Chen 1 , Hongquan Yu 1 , Zhonghua Zhang 1 , Cai Li 4 , Yunqian Li 1 1 Department of Neurosurgery, First Hospital of Jilin University, Changchun, China 2 Department of Obstetrics and Gynecology, First Hospital of Jilin University, Changchun, China 3 Department of Clinical Laboratory, Second Hospital of Jilin University, Changchun, China 4 Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun, China Correspondence to: Yunqian Li, e-mail: [email protected] Keywords: AMPK, AKT-mTOR, glioma stem cell, metformin, temozolomide Received: May 20, 2015 Accepted: September 14, 2015 Published: September 26, 2015 ABSTRACT Glioblastoma (GBM) is the most frequent and aggressive brain tumor in adults. In spite of advances in diagnosis and therapy, the prognosis of patients with GBM has remained dismal. The fast recurrence and multi-drug resistance are some of the key challenges in combating brain tumors. Glioma stem cells (GSCs) which are considered the source of relapse and chemoresistance, the need for more effective therapeutic options is overwhelming. In our present work, we found that combined treatment with temozolomide (TMZ) and metformin (MET) synergistically inhibited proliferation and induced apoptosis in both glioma cells and GSCs. Combination of TMZ and MET significantly reduced the secondary gliosphere formation and expansion of GSCs. We first demonstrated that…
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