Autophagy inhibition promotes paclitaxel-induced apoptosis in cancer cells
Autophagy inhibition promotes paclitaxel-induced apoptosis in cancer cells
复制标题
自噬抑制促进紫杉醇诱导的癌细胞凋亡
DOI：
10.1016/j.canlet.2011.03.026
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发表时间：
2011-08-28
期刊：
影响因子：
9.7
通讯作者：
Yuan, Huiqing
中科院分区：
文献类型：
--
作者：
Xi, Guangmin;Hu, Xiaoyan;Yuan, Huiqing
紫杉醇已被证明是一种有效的有丝分裂抑制剂和凋亡诱导剂，用于治疗侵袭性恶性肿瘤。在本文中，我们提供了一系列的证据表明，紫杉醇促进凋亡细胞死亡伴随着诱导A549细胞自噬。紫杉醇处理可导致酸性囊泡细胞器（AVO）的形成，诱导Atg 5、Beclin 1和微管相关蛋白1轻链3（LC 3）的表达，以及绿色荧光蛋白（GFP）标记的LC 3预转染的A549细胞中点状荧光信号的增加。有趣的是，紫杉醇介导的凋亡细胞死亡进一步加强预处理与自噬抑制剂3-甲基腺嘌呤（3-MA）或小干扰RNA对自噬基因beclin 1。这些结果表明，紫杉醇诱导的自噬反应发挥了保护作用，阻止最终的细胞死亡，抑制自噬可能是一个积极的策略，以提高紫杉醇作为一种抗肿瘤药物的化疗效果。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Paclitaxel has been demonstrated to be an effective mitotic inhibitor and apoptosis inducer to treat aggressive malignancies. In this paper, we have provided a line of evidence that promotion of apoptotic cell death by paclitaxel was accompanied with induction of autophagy in A549 cells. Paclitaxel treatment could lead to the formation of acidic vesicular organelles (AVOs), the induction of Atg5, Beclin 1 and microtubule-associated protein 1 light chain 3 (LC3) expressions, and the increase of punctate fluorescent signals in A549 cells pre-transfected with green fluorescent protein (GFP)-tagged LC3. Interestingly, paclitaxel-mediated apoptotic cell death was further potentiated by pretreatment with autophagy inhibitor 3-methyladenine (3-MA) or small interfering RNA against the autophagic gene beclin 1. These findings suggest that paclitaxel-elicited autophagic response plays a protective role that impedes the eventual cell death, and inhibition of autophagy could be an adjunctive strategy for enhancing chemotherapeutic effect of paclitaxel as an antitumor agent. (C) 2011 Elsevier Ireland Ltd. All rights reserved.