Combination of the mTOR inhibitor RAD001 with temozolomide and radiation effectively inhibits the growth of glioblastoma cells in culture

mTOR 抑制剂 RAD001 与替莫唑胺和放射疗法相结合可有效抑制培养胶质母细胞瘤细胞的生长

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作者:Hélène Burckel, Elodie Josset, Jean-Marc Denis, John Gueulette, Jakobus Slabbert, Georges Noël, Pierre Bischoff

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.

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