益康唑诱导HL-60白血病细胞内质网应激反应性细胞凋亡

Induction of Endoplasmic Teticulum Stress-related Apoptosis in HL-60 Leukemic Cells

目的研究唑类抗真菌药物益康唑(Ec)的抗白血病作用及其机制。方法将12μmol/LEc、0.1μmol/L倍半萜烯酯(Tg)和0.2μg/ml依霉素(Tu)作用于体外培养的人急性髓细胞性白血病细胞HL60,利用细胞核荧光染色进行形态学观察,Westernblot法检测分子伴侣蛋白(GRP78)和胱天蛋白酶(Caspase)的表达。结果HL60细胞经Ec,Tg和Tu处理后,细胞呈典型的凋亡形态,凋亡率分别为94%、63%和85%。分子伴侣蛋白GRP78的表达明显增加,位于内质网的Caspase12被活化。结论Ec可诱导人白血病HL60细胞内质网应激反应性细胞凋亡,凋亡的发生与蛋白质合成抑制、Caspase12的活化有关。

Objective To investigate the anti-leukemic role of econazole （Ec） and the mechanism. Methods The in vitro cultured HL-60 cells were treated with Ec （12μmol/L）, thapsigargin （Tg, 0.1μmol/L） or tunicamycin （Tu, 0.2μg/ml） respectively. Morphological analysis was performed by using nuclear fluorescent staining. Western blot was used to detect the expression of GRP78 and Caspase. Results After the HL-60 cells were treated with Ec, Tg or Tu respectively, a typical apoptotic morphology appeared, and the apoptotic rate was 94%, 63% and 85% respectively （all P〈0.01）. The expression of GRP78 was significantly increased and the Caspase in endoplasmic reticulum was activated. Conclusion Ec can induce endoplasmic reticulum stress-related apoptosis in HL-60 cells. The underlying mechanisms are protein synthesis inhibition through eIF2α phosphorylation and Caspase 12 activation.