博安霉素抗人肝癌的作用及其作用机制的研究  

Study on the effect of boanmycin against human-hepatoma BEL-7402 cells and its mechanism in molecular level

作　　者：张宏印[1] 谢忠[2] 李电东[2] 

机构地区：[1]北京大学医院,北京100871 [2]中国医学科学院中国协和医科大学医药生物技术研究所,北京100050

出　　处：《中国新药杂志》2001年第10期749-752,共4页Chinese Journal of New Drugs

摘　　要：目的 :研究新抗肿瘤抗生素博安霉素 (BAM )在体外的抗人肝癌的作用及其分子机制。方法 :采用细胞克隆形成法和NAG酶反应测定BAM抗肝癌作用 ,利用 [3H]标记物参入法测定BAM对肝癌细胞大分子合成的作用 ,利用斑点杂交检测BAM对肝癌细胞相关癌基因和抗癌基因表达的影响 ,利用中性凝胶电泳分析DNA损伤后的修复情况。结果 :BAM作用于BEL 740 2细胞克隆形成的最小IC50 为 8.6× 10 -9mol·L-1;对BEL 740 2细胞的杀伤的IC50 为 6 .2× 10 -6mol·L-1,表现出很强的抗肿瘤作用和良好的剂量 效应关系。对BEL 740 2细胞的DNA ,RNA和蛋白质合成均有强抑制作用 ,以抑制DNA和Pro合成的作用较强。在 0 .1～ 10 μmol·L-1浓度时 ,BAM明显抑制人肝癌细胞的c myc,N ras和p5 3基因的表达。BAM造成的人肝癌细胞DNA的损伤难以修复。 结论 :BAM是对人肝癌有效的抗肿瘤抗生素 ,其作用的分子机制与培洛霉素 (PEP)相似。Objectvie:The effects of boanmycin(BAM) against hu ma n hepatoma,BEL 7402 cells,and its mechanism in molecular level were studied in vitro .Methdos:The cellular clonogenic assay and NAG method were used for exa mining the effect of anti tumor.The big molecular synthesis,the expression onco gene and antioncogene,and the DNA damage were investigated with incorporation of some objects labeled with [JH3,D,Z],with dot blot and with neutral gel electrophoresis,respectively.Results: IC 50 of BAM with clonogenic assay and with NAG metho d was 8.6×10 -9 mol·L -1 and 6.2×10 -6 mol·L -1 ,respectiv ely.It showed high anticancer activities and obvious dose effect relationship.T he experiment indicated that BAM strongly inhibited cellular DNA,RNA and protein synthesis,but the effects of inhibiting cellular DNA and protein synthesis were more strongly than RNA synthesis.By dot blot of total RNA isolated from BEL 74 02 cell treated with BAM at 10 μmol·L -1 ,the expressions of c myc,N ras and p53 gene were strongly inhibited.Double strand cleavage DNA in repairing w as analyzed by neutral gel electrophoresis.This result indicated that DNA damage in BEL 7402 cells,which was incubated with BAM for 1 hour,was unable to repair itself.Conclusion:The results suggested that BAM was extensive antitumor anti biotic with high potency and was worthy to be further studied.

关 键 词：博安霉素 抗肿瘤抗生素 肝癌 BAM 

分 类 号：R979.14[医药卫生—药品] R735.7[医药卫生—药学]