烯二炔类抗生素卡利奇霉素抗肿瘤作用机制研究进展  

The mechanisms of action of enediyne antitumor antibiotic calicheamicins

作　　者：张文军[1] 李电东[1] 邵荣光[1] 

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所,北京100050

出　　处：《中国新药杂志》2008年第10期815-820,共6页Chinese Journal of New Drugs

基　　金：国家自然科学基金(30472107);国家重点基础研究发展计划(973计划)项目(2002CB513108)

摘　　要：卡利奇霉素(calicheamicins,CLM)是从稀有放线菌小单孢菌Micromonospora echinospora spp calichensis发酵液中分离得到的烯二炔类抗肿瘤抗生素。CLM的生物活性浓度<1pg·mL-1,对白血病如淋巴细胞白血病P388和L1210细胞以及实体瘤如结肠癌26和黑色素瘤B-16细胞有极强的杀伤作用。CLM生物活性的发挥主要通过与细胞DNA特异序列的小沟结合,直接断裂细胞DNA,进一步诱导肿瘤细胞凋亡,同时,CLM对细胞RNA也有非特异性的损伤作用。CLM与抗CD33单抗偶联物Mylotarg是第一个被FDA批准用于肿瘤治疗的单抗导向药物,已在临床应用。文中综述了CLM对肿瘤细胞作用机制的最新研究进展。Calicheamicins（CLM） , one of the enediyne antitumor antibiotics, was isolated from fermentation broth of Micromonospora echinospora spp calichensis. The bioactive concentration of CLM is 〈 1 pg·mL^-1 and it possesses excellent potency against murine tumors P388, L1210 leukemias, and solid neoplasms such as colon 26 and B16 melanoma. This compound is thought to exert their biological activities by damaging DNA and inducing cell apoptosis at very low concentrations by binding in the minor groove of DNA with specific sequences. Besides, the suppressogenicity of CLM correlates with a rapid and non-selective degradation of RNA. In clinical application of Gemtuzumab ozogamicin （Mylotarg） is an immunoconjugate targeted against CD33 overexpressed in myeloid leukemic blasts. In this paper, we review the mechanisms of action of enediyne antitumor antibiotic CLM.

关 键 词：卡利奇霉素 DNA断裂 细胞凋亡 RNA断裂 

分 类 号：R979.14[医药卫生—药品]