酪氨酸激酶抑制剂 Herbimycin A 联合化疗药物对 K562 细胞凋亡的影响

目的：探讨慢性髓细胞白血病（ＣＭＬ）细胞抗凋亡机制和诱导ＣＭＬ细胞凋亡的有效方法。方法：采用Ｋ５６２细胞培养，观察酪氨酸激酶抑制剂ＨｅｒｂｉｍｙｃｉｎＡ（ＨＭＡ）联合化疗药物对ＣＭＬ细胞凋亡的影响，探讨ＨＭＡ对ＣＭＬ细胞的作用。结果：ＨＭＡ或化疗药物单独应用可抑制Ｋ５６２细胞增殖，但不能明显诱导其凋亡。ＨＭＡ能明显增强化疗药诱导Ｋ５６２细胞凋亡。加入外源性巯基化合物阻断ＨＭＡ与酪氨酸激酶的结合可完全取消这种作用。结论：ＨＭＡ通过抑制ＣＭＬ细胞内酪氨酸激酶活性促进细胞凋亡而增加对化疗药物的敏感性，表明酪氨酸激酶抑制剂作为治疗ＣＭＬ药物具有潜在的应用价值。

Effect of combination of herbimycin A,an inhibitor of tyrosine kinase,and chemotherapeutic agents on apoptosis of K562 cells

Objective:To explore the anti apoptotic mechanism and the apoptosis inducing method in chronic myeloid leukemia (CML) cells. Methods:K562 cell line was used to observe the effect of combination of herbimycin A (HMA),a tyrosine kinase inhibitor,and chemotherapeutic agents on the induction of apoptosis.Results:HMA or chemotherapeutic agents could inhibit the proliferation but not significantly induce apoptosis of K562 cells.However,HMA significantly enhanced apoptosis when combined with chemotherapeutic agents .Addition of sulfhydryl compound to the cultures to conjugate HMA completely abrogated this enhancing effect on K562 cells.Conclusion:HMA increases the sensitivity of CML cells to chemotherapeutic agents by inactivating tyrosine kinase activity.It is promising that combination of HMA with conventional chemotherapeutic drugs in the treatment of CML.