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.
Anticancer Res. 2013 May;33(5):1845-51.
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.
我们研究了哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂 RAD001 和替莫唑胺联合应用对体外培养的胶质母细胞瘤细胞系 U-87 生长和细胞死亡的影响。替莫唑胺浓度增加时，细胞增殖逐渐减少，而添加 RAD001 则明显增强和延长了这种减少。虽然这种联合治疗仅导致低水平的细胞凋亡，但它导致自噬性细胞死亡明显增强。当与γ射线照射联合使用时，获得了整体细胞毒性的显著增强，提示这种多管齐下的方法治疗胶质母细胞瘤的疗效。RAD001 强烈促进替莫唑胺诱导的自噬，自噬似乎是胶质母细胞瘤的主要细胞死亡形式。将这些联合化疗与放疗联合应用可能有助于治疗这些难以治疗的恶性肿瘤。
