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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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| Authors: | 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 |
| Affiliation: | aDepartment 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 bDepartment of Oral Pathology, Okayama University, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8525, Japan cDepartment of Oral Microbiology, Okayama University, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8525, Japan dDepartment of Radiology, Okayama University, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho,Okayama 700-8525, Japan eDepartment of Surgical Oncology, Okayama University, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8525, Japan |
| Abstract: | 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. |
| Keywords: | MGMT CDDP O6-BG Oral cancer |
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