摘要
从我国湖北潜江县土壤分离的一株链霉菌产生的Ｃ１０２７是大分子肽类抗生素，其发色基团是新的烯二炔化合物。研究表明，抗生素Ｃ１０２７对肿瘤细胞有强烈杀伤作用。Ｃ１０２７在精原细胞法检测中显示高度活性，比阿霉素、丝裂霉素Ｃ等强５００倍。由发色基团和蛋白质两部分构成的Ｃ１０２７分子可以拆分与重建；而重建的Ｃ１０２７分子同样具有很强的活性。在可耐受剂量，Ｃ１０２７对移植性小鼠结肠癌２６以及对移植于裸鼠的人体肝癌和盲肠癌均有显著的疗效。
Antitumor antibiotic C1027,produced by Streptomycesglobisporus C1027 from a soil sample collected in Qianjiang County,Zh-ejiang Province,China,was detected by use of spermatogonial assayduring the screening of fermentation liquors.The C1027 molecule co- nsists of an apoprotein of 110 amino acid residues and an enediynechromophore. C1027 showed extremely potent cytotoxicity to cultured ca- ncer cells Determined by clonogenic assay lvith gastric cancer BGC-823cells,IC50 of C1027 was 1.5 ×10-17 mol/L; whereas IC50 values ofAdriamycin,Cisplatin and Methotrexate were 2.0 ×10-9 mol/L,2.0 ×10-8mol/L and 1.5 ×10-8 mol/L,respectively.Spermatogonial assay,a prescr-een for dctection of antitumor agents,was highly sensitive to C1027 witha minimum effective concentration of 0.004 μg/ml,approximately 500-foldlower than that of Adriamycin,Actinomycin D,Daunomycin or Mito-mycin C,The chromophore,an active part of the C1027 molecule,Wasseparated from and reunted with the apoprotein The reconstituted C1027remained fully its activity, being as potent as natural C1027 in cy-totoxicity.The association of chromophore and apoprotein was ratherspecific;as shown,IgG could not bind to thC chromophore and BSA(b-ovine serum aibumin)could not replace the aponrotein from C1027 mole-cule. C1027 markedly suppressed the growth of transplantable colon ca-ncer 26 in mice、At dose of 0.1 mg/kg,iv,×3,tumor inhibition ratereached 94%(P<0.01),Single iv dose of 0.1mg/kg inhibited tumor gro-wth by 76%,more effeetive,than Epirubicin and Mitomycin C as compar-ed at equitoxic dose levels.At tolerable doses,C1027 exerted remarkableinhibition on the growth of human hepatoma and colon cancer xenograf-ts in athymic mice.
出处
《中国抗生素杂志》
CAS
CSCD
北大核心
1994年第2期164-168,F003,共6页
Chinese Journal of Antibiotics
基金
国家自然科学基金
关键词
抗生素
C1027
烯二炔
抗肿瘤作用
Antitumor antibiotic C1027
Enediyne
Human tumor xenograft
