Specific mTOR inhibitor rapamycin enhances cytotoxicity induced by alkylating agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) in human U251 malignant glioma cells
作者： Kazuhiro Tanaka , Takashi Sasayama , Katsu Mizukawa , Atsufumi Kawamura , Takeshi Kondoh
DOI: 10.1007/S11060-007-9371-X
关键词:
摘要: Loss of the PTEN tumor suppressor gene and amplification epidermal growth factor receptor (EGFR), which is common in malignant gliomas, result activation mammalian target rapamycin (mTOR). Rapamycin a highly specific inhibitor mTOR induces cytostatic effect various glioma cell lines. DNA-damaging agents such as nitrosourea are widely used treatment; therefore, we investigated on death combination with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU, nimustine hydrochloride) human cells. In U251 (U251MG) cells, confirmed that enhanced ACNU-induced apoptosis. We found rapamysin inhibited p21 induction, knocking down protein by siRNA apoptosis U251MG Furthermore, adenovirus-mediated over-expression rescued cells from induced ACNU rapamycin. Finally, treatment intracerebral xenografts vivo resulted statistically prolonged median survival (P < 0.05). These results suggest may be efficacious gliomas.
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