title: Combination of the mTOR inhibitor RAD001 with temozolomide and radiation effectively inhibits the growth of glioblastoma cells in culture.
abstract: The present in vitro study aimed to assess the effects of combining the mTOR inhibitor RAD001 and temozolomide (TMZ) together with irradiation by either low-linear energy transfer (LET) radiation (γ-rays) or high-LET radiation (fast neutrons) on the growth and cell survival of the human glioblastoma cell line U-87. We observed a strong decrease in cell proliferation along with a concomitant increase in cell death as a function of the radiation dose. As expected, high-LET radiation was more effective and induced more sustained damage to DNA than low-LET radiation. While RAD001 in association with TMZ induced autophagic cell death, additional combination with either type of radiation did not further increase its occurrence. On the contrary, apoptosis remained at a low level in all experimental groups.
authors.affiliation: EA 3430, University of Strasbourg, Centre Paul Strauss, Strasbourg, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Burckel
authors.affiliation: EA 3430, University of Strasbourg, Centre Paul Strauss, Strasbourg, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Josset
authors.affiliation: MIRO, Catholic University of Louvain, Brussels, Belgium.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Denis
authors.affiliation: MIRO, Catholic University of Louvain, Brussels, Belgium.
authors.forename: John
authors.initials: J
authors.lastname: Gueulette
authors.affiliation: iThemba LABS, Somerset West, South Africa.
authors.forename: Jakobus
authors.initials: J
authors.lastname: Slabbert
authors.affiliation: EA 3430, University of Strasbourg, Centre Paul Strauss, Strasbourg, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Noël
authors.affiliation: EA 3430, University of Strasbourg, Centre Paul Strauss, Strasbourg, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bischoff
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004307:Dose-Response Relationship, Radiation; D000068338:Everolimus; D005720:Gamma Rays; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006657:Histones / Q000378:metabolism; D006801:Humans; D018499:Linear Energy Transfer; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D000077204:Temozolomide
chemical_list: C468783:H2AX protein, human; D006657:Histones; D003606:Dacarbazine; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus; D000077204:Temozolomide