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Anticancer Res. 2013 May;33(5):1845-51.

The mTOR inhibitor RAD001 potentiates autophagic cell death induced by temozolomide in a glioblastoma cell line.

Author information

1
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.

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.

KEYWORDS:

Glioblastoma; RAD001; autophagy; temozolomide; γ-radiation

PMID:
23645729
[Indexed for MEDLINE]

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