ANTITUMOR EFFECT OF SARCNU IN A 0～6-METHYLGUANINE-DNA METHYLTRANSFERASE POSITIVE HUMAN GLIOMA XENOGRAFT MODEL

Objective:To assess whether novel analogue of nitrosoureas, 2-chloroethyl-3-sarcosinamide- 1 -nitrosourea (SarCNU), has antitumor effect to 0～6-methylguanine-DNA methyltransferase (MGMT) positive tumors in vivo. Methods:MGMT positive human glioma cell line SF-767 xenografts in nude mice were treated with SarCNU. The antitumor efficacy of SarCNU was compared with the results of 1, 3-bis (2-chloroethyl) - 1 -nitrosourea (BCNU) treatment with or without 0～6-benzylguanine (0～6-BG) preadministration. Results: Since the SF-767 is MGMT strongly positive, BCNU treatment alone did not result in a satisfactory anticancer effect. As expected, 0～6-BG by depleting MGMT activity, significantly enhanced BCNU antitumor efficacy (P<0.001). More interestingly, SarCNU treatment alone had a better antitumor effect than 0～6-BG plus BCNU treatment (F=51.7, P=0.00036). Conclusion: Since SarCNU enters cells via extraneuronal monoamine transporter (EMT), the enhanced antitumor activity of SarCNU in this MGMT positive human tumor xenograft model may be due to the presence of EMT in SF-767. SarCNU may be used as an alternative treatment for MGMT positive tumors, specifically for tumors expressing EMT