| 张心桐,戚欣,李静＊.Hsp90抑制剂HDN-1诱导急性早幼粒细胞白血病NB4细胞凋亡的研究[J].中国海洋药物,2017,36(4):35-40. |
| Hsp90抑制剂HDN-1诱导急性早幼粒细胞白血病NB4细胞凋亡的研究 |
| A research of apoptosis-inducing effects of APL cells NB4 by an Hsp90 inhibitor HDN-1 |
| 投稿时间：2017-01-17 修订日期：2017-03-15 |
| DOI： |
| 中文关键词: HDN-1 NB4细胞 PML-RARα 细胞凋亡 |
| English Keywords:HDN-1 NB4 cells PML-RARα Apoptosis |
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| 中文摘要: |
| 目的：探讨南极土壤来源真菌的次级代谢产物HDN-1对人急性粒细胞白血病NB4细胞的增殖抑制,诱导凋亡作用及其机制。方法：采用MTT法检测HDN-1对NB4细胞的增殖抑制作用；DNA结合染料Hoechst 33324染色,Western Blot实验,流式细胞仪检测细胞凋亡以及凋亡相关蛋白的变化。结果：HDN-1能显著抑制NB4细胞的增殖,并呈剂量－时间依赖性；HDN-1作用后,细胞核形态发生明显变化且流式细胞仪分析表明NB4细胞凋亡数量明显增加；HDN-1可引起Caspase-3, 8, 9激活,bid减少,线粒体中凋亡蛋白Bcl-2, Mcl-1的表达降低,以及γ-H2AX、Parp剪切带增加。但是NB4细胞中融合蛋白PML-RARα的表达不能被HDN-1所抑制。结论：HDN-1诱导凋亡是通过Caspase依赖的线粒体途径和死亡受体途径共同介导的,PML-RARα不是Hsp90的客户蛋白,其诱导凋亡机制可能是通过抑制Hsp90的其它蛋白表达进行的。 |
| English Summary: |
| Objective To investigate the mechanisms of proliferation inhibition and inducing apoptosis of human acute promyelocytic leukimic cells NB by HDN-1, a secondary metabolites of antarctic soil fungi. Methods MTT assay was applied to examine the effect of HDN-1 on the proliferation inhibition of NB4 cells. Hoechst 33324 staining, Western Blot and FCM were used to detect the apoptosis of NB4 cells. Result HDN-1could inhibit the proliferation and induce apoptosis in NB4 cells in time- and dose-dependent manners. Typical morphological changes were observed under the treatment of HDN-1. Western Blot showed cleavage of the caspase-3,8,9 zymogen protein and an 89KDa subunit cleavage product of ADP-ribose Parp after treatment of HDN-1. Moreover, Western Blot also revealed that the expression of anti-apoptotic protein bcl-2 and Mcl-1 was up-regulated, and PML-RARα cannot degraded after treatment of HDN-1.FCM figures also showed the effect of HDN-1 on the proliferation inhibition of NB4 cells. Conclusion All these results suggest that HDN-1 induces apoptosis of NB4 cells by caspase-dependent pathway and death receptor pathway. PML-RARα isn’t client protein of Hsp90, so the mechanism of HDN-1-induced apoptotic could be inhibition other client protein of Hsp90. |
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