高三尖杉酯碱通过抑制P210^bcr／abl诱导K562细胞凋亡

为探讨高三尖杉酯碱（ｈｏｍｏｈａｒｒｉｎｇｔｏｎｉｎｅ，ＨＨＴ）抗慢性髓细胞白血病（ＣＭＬ）的机制，以ＣＭＬ细胞系Ｋ５６２细胞为对象，应用ＡｎｎｅｘｉｎＶ－ＰＩ双标志和Ｗｅｓｔｅｒｎ印迹杂交技术，观察ＨＨＴ对细胞凋亡和Ｐ２１０＾ｂｃｒ／ａｂｌ癌蛋白的影响。结果表明，５－２０ｎｇ／ｍｌ浓度的ＨＨＴ可诱导Ｋ５６２细胞凋亡，但随着药物浓度的增加细胞出现坏死性死亡，ＨＨＴ可使细胞内融合蛋白Ｐ２１０＾ｂｃｒ／ａｂｌ的含量约减少７０％，而对正常存在于细胞内的Ｐ１４５＾ｃ－ａｂｌ无影响，上述结果证实，ＨＨＴ通过对Ｐ２１０＾ｂｃｒ／ａｂｌ的定向抑制作用促进ＣＭＬ细胞凋亡，这可能是其抗ＣＭＬ的分子机制。本研究为ＨＨＴ在临床上的进一步应用提供了实验基础。

Homoharringtonine Induces Apoptosis of K562 Cells through Inhibition of P210bcr/abl

In this study, the underlying antileukemic mechanisms of homoharringtonine (HHT) were investigated. K562 cell line was used to observe the effects of HHT on the induction of apoptosis and on the expression of the specific chimeric protein P210 bcr/abl, as evaluated by flow cytometric annexin V-PI dual labeling technique and Western blot. The results showed that HHT induced K562 cells to apoptotic death at the concentrations of 5-20 ng/ml, and some of the cells became necrotic when exposed to a higher concentration. The amount of P210 bcr/abl oncoprotein was decreased by approximately 70% when the cells were exposed to HHT for 48 hours, however, that of its partner P145 c-abl proto-oncoprotein was not affected. It is clear from the study that HHT is an inhibitor of P210 bcr/abl oncoprotein and therefore promotes the apoptosis of CML cells. It could be promising that HHT be used extensively in the chemotherapy of patients with CML.