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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Apoptosis / drug effects
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Apoptosis / radiation effects
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Brain Neoplasms / drug therapy*
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Brain Neoplasms / pathology
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Brain Neoplasms / radiotherapy*
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Cell Proliferation / drug effects
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Cell Proliferation / radiation effects
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Cell Survival / drug effects
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Cell Survival / radiation effects
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DNA Damage / drug effects
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DNA Damage / radiation effects
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Dacarbazine / administration & dosage
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Dacarbazine / analogs & derivatives
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Dose-Response Relationship, Radiation
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Everolimus
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Gamma Rays
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Glioblastoma / drug therapy*
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Glioblastoma / pathology
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Glioblastoma / radiotherapy*
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Histones / metabolism
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Humans
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Linear Energy Transfer
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Sirolimus / administration & dosage
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Sirolimus / analogs & derivatives
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TOR Serine-Threonine Kinases / antagonists & inhibitors
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Temozolomide
Substances
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H2AX protein, human
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Histones
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Dacarbazine
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Everolimus
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MTOR protein, human
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TOR Serine-Threonine Kinases
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Sirolimus
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Temozolomide