Maki Yu, Murakami Jun, Asaumi Jun-ichi, Tsujigiwa Hidetsugu, Nagatsuka Hitoshi, Kokeguchi Susumu, Fukui Kazuhiro, Kawai Noriko, Yanagi Yoshinobu, Kuroda Masahiro, Tanaka Noriaki, Matsubara Nagahide, Kishi Kanji
Department of Oral and Maxillofacial Radiology, Field of Tumor Biology, Okayama University, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8525, Japan.
Oral Oncol. 2005 Nov;41(10):984-93. doi: 10.1016/j.oraloncology.2005.05.011. Epub 2005 Jul 25.
The DNA repair enzyme O6-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 lines. CDDP depleted MGMT protein and mRNA levels in all four cell lines. 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 lines with high MGMT expression were resistant to both agents. Furthermore, the addition of the MGMT inhibitor, O6-benzylguanine (O6-BG), invariably enhanced CDDP sensitivity. CDDP depleted MGMT expression, and CDDP sensitivity was enhanced by O6-BG. These results provide valuable information about the relationship between MGMT expression and CDDP sensitivity in oral cancer chemotherapy.
DNA修复酶O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）可调节烷化剂的有效性。然而，MGMT与其他药物敏感性之间的关系尚未得到探索。在本研究中，检测了四种人类口腔癌细胞系中MGMT表达与细胞对铂类药物顺铂（CDDP）敏感性之间的关联。CDDP使所有四种细胞系中的MGMT蛋白和mRNA水平降低。两个MGMT低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MGMT高表达的细胞系对这两种药物均耐药。此外，添加MGMT抑制剂O6-苄基鸟嘌呤（O6-BG）始终会增强CDDP敏感性。CDDP降低了MGMT表达，且O6-BG增强了CDDP敏感性。这些结果为口腔癌化疗中MGMT表达与CDDP敏感性之间的关系提供了有价值的信息。
