N-磷酰化二肽甲酯诱导K562细胞凋亡  

Apoptosis of K562Cell Induced by N-p hosphoryl Dipeptide Methyl Ester

作　　者：牛艳玲[1] 曹胜利[1] 蒋宇扬[1] 杜伟[1] 赵玉芬[1] 

机构地区：[1]清华大学生命科学与工程研究院化学系生命有机磷化学教育部重点实验室,北京100084

出　　处：《癌症》2002年第8期823-827,共5页Chinese Journal of Cancer

基　　金：国家自然科学基金项目(No:20132020);北京市科委基金;清华工研院科技基金

摘　　要：背景与目的:磷被认为是生命代谢过程中的中心元素,许多N-磷酰化氨基酸和N-磷酰化肽具有重要的生物活性和药用价值,本实验研究N-磷酰化二肽甲酯诱导人慢性髓性白血病K562细胞凋亡作用。方法:采用四甲基偶氮唑盐还原法犤3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyl-tetrazoliumbromide,MTT犦检测15种N-磷酰化二肽甲酯对K562细胞的增殖抑制作用;用Hoechst33258染色后观察细胞核的形态学变化;DNA琼脂糖凝胶电泳、双染法和流式细胞术检测细胞凋亡。结果:MTT法筛选出细胞增殖抑制活性较好的化合物是(DIPP-L-Leu)2-L-Lys-OCH3,IC50为22.66μmol/L;Hoechst33258染色后细胞核出现明显的凋亡形态学变化;DNA琼脂糖凝胶电泳出现典型的梯状条带;流式细胞仪检测到早期的凋亡细胞。结论:(DIPP-L-Leu)2-L-Lys-OCH3能够诱导K562细胞凋亡。Background &Objective:Phosphorus plays a crucial role in me tabolism.Some N-phosphoryl amino a cids and N-phosphopeptides have importa nt biological activities and medicinal value.The current study was designed to investigate the apoptosis of K562cells induced b y N-phosphoryl dipeptide methyl ester.Method:Cell growth inhibition of K562cells induced by 15kinds of N-phosphoryl dipeptide methyl esters was analyzed by using MTT assay.The nuclei were stained by Hoechst 33258and the morphologic ch anges were observed.DNA agarose gel electrophoresis,double-staining,and flow cytomery were used to detect early ap optosis of K562cells.Result:(DIPP-L-Leu)2-L-Lys-OCH 3 was the compound screened with MTT method that had better growt h inhibiting activity with the IC 50 of 22.66μmol /L.Chromatin condensation and nuclear fragmentation were seen under fluorescence microscope in the cells treated with Hoechst 33258.DNA a garose gel electrophoresis showed nuclear fra gmentation(DNA ladder).Early apoptotic cells were also detected by flow cytometry.Conclusion:These results suggest that(DIPP-L-Leu) 2 -L-Lys-OCH 3 could induce the apoptosis of K562cells.

关 键 词：N-磷酰化二肽甲酯 细胞 细胞凋亡 K562 

分 类 号：R73-36[医药卫生—肿瘤]