IFN-beta down-regulates the expression of DNA repair gene MGMT and sensitizes resistant glioma cells to temozolomide.
IFN-beta down-regulates the expression of DNA repair gene MGMT and sensitizes resistant glioma cells to temozolomide.
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发表时间：
2005
期刊：
影响因子：
11.2
通讯作者：
A. Natsume;Dai Ishii;T. Wakabayashi;Takaya Tsuno;H. Hatano;M. Mizuno;J. Yoshida
中科院分区：
文献类型：
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作者：
A. Natsume;Dai Ishii;T. Wakabayashi;Takaya Tsuno;H. Hatano;M. Mizuno;J. Yoshida
烷化剂，如替莫唑胺，是用于恶性胶质瘤的最有效的细胞毒性药物之一，但反应仍然非常差。DNA修复蛋白O 6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）在细胞对烷化剂的抗性中起重要作用。IFN-β可以作为药物敏化剂，增强对各种肿瘤的毒性，并广泛与其他抗肿瘤药物如亚硝基脲联合使用。在这里，我们表明，IFN-β敏感神经胶质瘤细胞，港口的非甲基化MGMT启动子和耐替莫唑胺。通过寡核苷酸芯片和RNA干扰，我们揭示了IFN-β的增敏作用可能是由于通过诱导p53蛋白减弱MGMT表达。我们的研究表明，替莫唑胺的临床疗效可能会改善与IFN-β使用适当的剂量和管理计划的组合。
Alkylating agents, such as temozolomide, are among the most effective cytotoxic agents used for malignant gliomas, but responses remain very poor. The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) plays an important role in cellular resistance to alkylating agents. IFN-beta can act as a drug sensitizer, enhancing toxicity against a variety of neoplasias, and is widely used in combination with other antitumor agents such as nitrosoureas. Here, we show that IFN-beta sensitizes glioma cells that harbor the unmethylated MGMT promoter and are resistant to temozolomide. By means of oligonucleotide microarray and RNA interference, we reveal that the sensitizing effect of IFN-beta was possibly due to attenuation of MGMT expression via induction of the protein p53. Our study suggests that clinical efficacy of temozolomide might be improved by combination with IFN-beta using appropriate doses and schedules of administration.