二异丙氧基磷酰化亮赖叉肽甲酯诱导K562细胞凋亡

Apoptosis of K562 cells induced by diisopropylphosphoryl leucyl-lysine methyl ester

为寻找能特异性诱导肿瘤细胞凋亡的小分子诱导剂,研究了二异丙氧基磷酰化亮赖叉肽甲酯((DIPP-L-Leu)2-L-Lys-OCH3)对K562细胞的促凋亡作用。合成了(DIPP-L-Leu)2-L-Lys-OCH3,通过质谱、磷谱、氢谱和碳谱进行结构鉴定。通过MTT比色实验得到:该样品对K562细胞的半抑制浓度为22.66μmol.L-1。AO荧光染色、DNA琼脂糖凝胶电泳和Annexin -FITC/PI双染实验表明:该样品对K562细胞的增殖抑制作用是通过诱导细胞凋亡实现的。Caspase活性分析实验证明该样品是通过线粒体途径启动细胞凋亡。

This paper studies the apoptosis of K562 cells in diisopropylphosphoryl leucyl-lysine methyl ester ((DIPP-L-Leu)_2- L-Lys-OCH_3) to investigate special induces in tumor cells. (DIPP-L-Leu)_2-L-Lys-OCH_3 was synthesized, then verified by ESI-MS, ~31P NMR, ~1H NMR and ~13C NMR. The apoptosis was investigated using MTT assays, fluorescence microscopy, and AnnexinV-FITC flow cytometry analysis. The results show that (DIPP-L-Leu)_2-L-Lys-OCH_3 can induce apoptosis of K562 cells with an IC_50 of 22.66 μmol·L^-1. Specific caspase assays show that (DIPP-L-Leu)_2-L-Lys-OCH_3 induces apoptosis in K562 cells through the mitochondrial pathway.