BCR-ABL酪氨酸激酶抑制剂STI571选择性诱导K562细胞凋亡

Selective induction of apoptosis in K562 cells by a BCR-ABL tyrosine kinase inhibitor,STI 571

目的 探讨STI 5 71抑制慢性髓性白血病 (CML)细胞株增殖的机理及特异性。方法 选用非特异性的凋亡诱导剂阿霉素和BCR ABL阴性的白血病细胞株MO7E作为对照 ,观察两种抑制剂作用下两种细胞形态学的改变和胞浆DNA电泳图的改变。结果 STI5 71可诱导K5 6 2细胞凋亡 ,而对MO7E细胞无致凋亡作用 ;阿霉素可诱导MO7E细胞凋亡 ,而对K5 6 2细胞无诱导凋亡作用。结论 STI 5 71通过阻断BCR ABL酪氨酸激酶活力 ,促进K5 6 2细胞凋亡达到抑制细胞增殖的目的 ,而对不表达BCR ABL的细胞株无诱导凋亡的作用 ,提示STI5

Objective To study the mechanism and specificity of the anti proliferative effect of STI*!571 on BCR ABL positive cell line.Methods We selected a BCR ABL positive human leukemia cell line K562 in our experiments and also used a BCR ABL negative human leukemia cell line MO7E as a negative control.Cells were treated with STI*!571 or Adriamycin for 18 hours and then cell morphology and DNA electrophoresis were observed.Results STI*!571 induced apoptosis of K562 cells but not MO7E cells and on the other hand Adriamycin induced apoptosis of MO7E cells but not K562 cells.Conclusion STI*!571 shows anti proliferative effects on BCR ABL positive cells by blocking the activity of BCR ABL tyrosine kinase and induces the cell apoptosis.It has little inhibitory effects on BCR ABL negative cells.We concluded here that STI*!571 inhibitory effect is specific on BCR ABL signal transduction pathway.