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双氢青蒿素诱导的细胞凋亡并不依赖于 Bim 向人肺腺癌细胞内质网的易位。

Dihydroarteminsin-induced apoptosis is not dependent on the translocation of Bim to the endoplasmic reticulum in human lung adenocarcinoma cells.

机构信息

MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou, 510631, China.

出版信息

Pathol Oncol Res. 2012 Oct;18(4):809-16. doi: 10.1007/s12253-012-9508-x. Epub 2012 Mar 7.

Abstract

Bim, a proapoptotic BH3-only member of Bcl-2 family, has been considered to play an important role in initiating mitochondrial apoptotic pathway. Our previous studies have shown the ability of dihydroarteminsin (DHA) to induce apoptosis in human lung adenocarcinoma (ASTC-a-1) cells. In this study, we investigated the function of Bim during DHA-induced apoptosis in ASTC-a-1 and another human lung adenocarcinoma (A549) cell lines. Confocal imaging of single living cell expressing GFP-BimL showed the translocation of Bim to endoplasmic reticulum (ER) rather than mitochondria during DHA-induced apoptosis. Moreover, we also found that DHA induced ER stress and an increase of Bim protein levels. However, silencing Bim by short hairpin RNA did not inhibit DHA-induced caspase-9 activation and cell apoptosis. Taken together, our results demonstrate for the first time that DHA induces Bim translocation to ER, but DHA-induced apoptosis is not dependent on Bim in ASTC-a-1 and A549 cell lines.

摘要

Bim,Bcl-2 家族中的一种促凋亡 BH3 仅成员,被认为在启动线粒体凋亡途径中发挥重要作用。我们之前的研究表明二氢青蒿素(DHA)能够诱导人肺腺癌细胞(ASTC-a-1)凋亡。在这项研究中,我们研究了 Bim 在 DHA 诱导的 ASTC-a-1 和另一种人肺腺癌细胞(A549)系中凋亡过程中的作用。表达 GFP-BimL 的单个活细胞的共焦成像显示,在 DHA 诱导的凋亡过程中,Bim 向内质网(ER)而不是线粒体易位。此外,我们还发现 DHA 诱导 ER 应激和 Bim 蛋白水平增加。然而,短发夹 RNA 沉默 Bim 并不能抑制 DHA 诱导的 caspase-9 活化和细胞凋亡。总之,我们的结果首次表明,DHA 诱导 Bim 向 ER 易位,但在 ASTC-a-1 和 A549 细胞系中,DHA 诱导的凋亡不依赖于 Bim。

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