title: The mTOR inhibitor RAD001 potentiates autophagic cell death induced by temozolomide in a glioblastoma cell line.
abstract: We have studied the consequences of the combination of the mammalian target of rapamycin (mTOR) inhibitor RAD001 and temozolomide on the growth and cell death of the glioblastoma cell line U-87 in vitro. A progressive decrease of cell proliferation was recorded with increasing concentrations of temozolomide, which was markedly reinforced and prolonged by the addition of RAD001. While this combination treatment resulted in only a low level of apoptosis, it led to a pronounced enhancement of autophagic cell death. When combined with γ-ray irradiation, a significant reinforcement of the overall cytotoxicity was obtained, suggesting the efficacy of such a multipronged approach for the treatment of glioblastoma. RAD001 strongly contributes to the reinforcement of temozolomide-induced autophagy, which appears to represent a major form of cell death in glioblastoma. The association of such combined chemotherapies with radiotherapy could be useful for the management of these hard-to-treat malignancies.
authors: Université de Strasbourg, Centre régional de Lutte contre le Cancer Paul Strauss, 3 rue de la Porte de l'Hôpital, F-67085 Strasbourg Cedex, France.
authors: Elodie
authors: E
authors: Josset
authors: Hélène
authors: H
authors: Burckel
authors: Georges
authors: G
authors: Noël
authors: Pierre
authors: P
authors: Bischoff
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D001343:Autophagy; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D049109:Cell Proliferation / Q000187:drug effects* / Q000528:radiation effects; D002588:Cesium Radioisotopes; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004357:Drug Synergism; D000068338:Everolimus; D005434:Flow Cytometry; D005720:Gamma Rays; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D006801:Humans; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D000077204:Temozolomide; D014407:Tumor Cells, Cultured
chemical_list: D002588:Cesium Radioisotopes; D003606:Dacarbazine; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus; D000077204:Temozolomide
keywords: Glioblastoma; RAD001; autophagy; temozolomide; γ-radiation