Role of O-6-methylguanine-DNA methyltransferase and effect of O-6-benzylguanine on the anti-tumor activity of cis-diaminedichloroplatinum(II) in oral cancer cell lines

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.