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以中国人肿瘤细胞株和活检组织为材料 ,观察了O6 甲基鸟嘌呤 DNA 甲基转移酶 (MGMT)酶活性与亚硝脲药物耐药性之间的关系 ,证明MGMTmRNA高表达是产生耐药性的原因 ;体外和临床实验证明链脲菌素和苄基鸟嘌呤可以抑制MGMT酶活性 ,克服耐药性 ;体外实验证明反义寡聚核苷酸可以调节MGMT基因表达 ,逆转录病毒介导的反义RNA可以调节MGMTmRNA水平 ,克服耐药性 ;提出了以分析MGMT酶活性为依据 ,以调节酶活性和基因表达为手段 ,使用亚硝脲进行肿瘤预见性化疗的新方案。
The relationship between O6 methylguanine DNA methyltransferase (MGMT) enzyme activity and nitrosourea drug resistance was observed in Chinese human tumor cell lines and biopsy tissues, demonstrating that high expression of MGMT mRNA is responsible for drug resistance. Sexual causes; In vitro and in vitro studies demonstrate that streptozotocin and benzylguanine can inhibit MGMT enzyme activity and overcome drug resistance; In vitro experiments demonstrate that antisense oligonucleotides can regulate MGMT gene expression, and retrovirus-mediated The antisense RNA can regulate MGMT mRNA levels and overcome drug resistance. Based on the analysis of MGMT enzyme activity, a new scheme of tumor-predictive chemotherapy using nitrosourea is proposed by means of regulating enzyme activity and gene expression.