Role of O6-methylguanine-DNA methyltransferase and effect of O6-benzylguanine on the anti-tumor activity of cis-diaminedichloroplatinum(II) in oral cancer cell lines
Role of O6-methylguanine-DNA methyltransferase and effect of O6-benzylguanine on the anti-tumor activity of cis-diaminedichloroplatinum(II) in oral cancer cell lines
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DOI：
10.1016/j.oraloncology.2005.05.011
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发表时间：
2005-11-01
期刊：
影响因子：
4.8
通讯作者：
Kishi, K
中科院分区：
文献类型：
--
作者：
Maki, Y;Murakami, J;Kishi, K
DNA修复酶，O-6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）调节烷化剂的有效性。然而，MGMT和其他药物敏感性之间的关系尚未探讨。在本研究中，在四个人口腔癌细胞系中检测了MGMT表达与细胞对铂类药物CDDP敏感性之间的关系。CDDP在所有四种细胞中耗尽MGMT蛋白和mRNA水平。两个低MGMT表达的细胞系对烷化剂N-甲基-N '-硝基-N-亚硝基胍和CDDP敏感，而另外两个高MGMT表达的细胞系对这两种药物都有抗性。此外，MGMT抑制剂O-6-苄基鸟嘌呤（O-6-BG）的加入总是增强CDDP敏感性。CDDP使MGMT表达减少，O-6-BG使CDDP敏感性增强。这些结果为口腔癌化疗中MGMT表达与顺铂敏感性的关系提供了有价值的信息。(c)2005爱思唯尔有限公司保留所有权利。
The DNA repair enzyme, O-6-methylguanine-DNA methyltransferase (MGMT) modulates the effectiveness of alkylating agents. However, the relationship between MGMT and the sensitivities to other agents has not been explored. In the present study, the association between MGMT expression and the cellular sensitivity to the platinum agent, CDDP was examined in four human oral cancer cell tines. CDDP depleted MGMT protein and mRNA levels in all four cell tines. Two cell lines with low MGMT expression were sensitive to an alkylating agent, N-methyl-N'-nitro-N-nitrosoguanidine and CDDP, whereas two other cell tines with high MGMT expression were resistant to both agents. Furthermore, the addition of the MGMT inhibitor, O-6-benzylguanine (O-6-BG), invariably enhanced CDDP sensitivity. CDDP depleted MGMT expression, and CDDP sensitivity was enhanced by O-6-BG. These results provide valuable information about the relationship between MGMT expression and CDDP sensitivity in oral cancer chemotherapy. (c) 2005 Elsevier Ltd. All rights reserved.