Synergistic Effect of Perampanel and Temozolomide in Human Glioma Cell Lines

Journal of Personalized Medicine

Marta Maschio¹  Cristina Corno²  Emilio Ciusani²  Annachiara D’Urso²  Paola Perego³  Sara Donzelli⁴  Andrea Salmaggi⁵ 

[1] Center for Tumor-Related Epilepsy, UOSD Neuroncology Regina Elena National Cancer Institute Rome, 00161 Rome, Italy;Department of Diagnostic and Technology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy;Molecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy;Oncogenomic and Epigenetic Unit, Regina Elena National Cancer Institute, 00161 Rome, Italy;Stroke Unit-Department of Neurology, Manzoni Hospital,23900 Lecco, Italy;

关键词: glioblastoma;    perampanel;    AMPA receptors;    glutamate;   

DOI  :  10.3390/jpm11050390

来源: DOAJ

【 摘 要 】

Glioblastoma is characterized by a high proliferative rate and drug resistance. The standard of care includes maximal safe surgery, followed by radiotherapy and temozolomide chemotherapy. The expression of glutamate receptors has been previously reported in human glioma cell lines. The aim of this study was to examine the cellular effects of perampanel, a broad-spectrum antiepileptic drug acting as an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) glutamate receptor antagonist, alone or in combination with temozolomide. Four human glioma cell lines were exposed to different concentrations of perampanel and temozolomide, alone or in combination. The type of drug interaction was assessed using the Chou-Talalay method. Apoptosis, cell cycle perturbation, and glutamate receptors (GluRs) subunit expression were assessed by flow cytometry. Perampanel significantly inhibited the growth, inducing high levels of apoptosis. A strong synergistic effect of the combination of perampanel with temozolomide was detected in U87 and A172, but not in U138. Treatment with perampanel resulted in an increased GluR2/3 subunit expression in U87 and U138. Perampanel displays a pro-apoptotic effect on human glioblastoma cell lines when used alone, possibly due to increased GluR2/3 expression. The observed synergistic effect of the combination of temozolomide with perampanel suggests further investigation on the impact of this combination on oncologic outcomes in glioblastoma.

【 授权许可】

Unknown