ANTITUMOR EFFECT OF SARCNU IN A 06-METHYLGUANINE-DNA METHYLTRANSFERASE POSITIVE HUMAN GLIOMA XENOGRA

• 作 者: CHEN Zhong-ping PAN Jun HUANG Qiang SUN Zhi-fang ZHOU Li-ying WANG Ai-dong Lawrence C. PANASCI
• 机 构: Department of Neurosurgery/Neuro-Oncology, Tumor Hospital, Sun Yat-sen University of Medical Science
• 出 处: 中国癌症研究（英文版）
• 发表日期: 2000年1期
• 关键词: 2-chloroethyl-3-sarcosinamide-1-nitrosourea chemotherapy extraneuronal monoamine

To assess whether novel analogue of nitrosoureas, 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU), has antitumor effect to 06-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 06-benzylguanine (06-BG) preadministration. Results: Since the SF-767 is MGMT strongly positive, BCNU treatment alone did not result in a satisfactory anticancer effect. As expected, 06-BG by depleting MGMT activity, significantly enhanced BCNU antitumor efficacy (p<0.001). More interestingly, SarCNU treatment alone had a better antitumor effect than 06-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 altative treatment for MGMT positive tumors, specifically for tumors expressing EMT.