The activation of c-Jun NH₂-terminal kinase is required for dihydroartemisinin-induced autophagy in pancreatic cancer cells.
The activation of c-Jun NH₂-terminal kinase is required for dihydroartemisinin-induced autophagy in pancreatic cancer cells.
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双氢青蒿素诱导胰腺癌细胞自噬需要激活 c-Jun NH2 末端激酶
DOI：
10.1186/1756-9966-33-8
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发表时间：
2014-01-18
期刊：
影响因子：
--
通讯作者：
Sun B
中科院分区：
文献类型：
--
作者：
Jia G;Kong R;Ma ZB;Han B;Wang YW;Pan SH;Li YH;Sun B
背景c-Jun氨基末端激酶（JNK）在应激性细胞环境如化疗和氧化应激中被强烈激活。自噬是一种蛋白质降解系统，其中形成称为自噬体的双膜液泡。自噬相关基因Beclin 1在这一过程中起着关键作用。我们以前发现，自噬是由双氢青蒿素（DHA）诱导胰腺癌细胞。方法采用细胞活力测定和CCK-8法检测细胞增殖，用小分子干扰RNA（siRNA）敲除c-Jun氨基末端激酶（JNK 1/2）基因，用流式细胞仪检测细胞凋亡，用流式细胞仪检测细胞凋亡率。Western blot检测LC 3、JNK、Beclin 1、caspase 3和β-actin蛋白表达，流式细胞仪检测细胞内活性氧（ROS）的产生;结果在本研究中，我们探讨了DHA和Beclin 1表达在自噬中的作用。DHA处理的细胞表现出自噬特征，DHA还激活JNK通路并上调Beclin 1的表达。相反，阻断JNK信号传导抑制Beclin 1上调。发现JNK活化主要依赖于DHA处理产生的活性氧（ROS）。此外，JNK通路抑制和Beclin 1沉默防止DHA诱导的自噬的诱导。结论这些结果表明，DHA诱导的自噬需要JNK介导的Beclin 1的表达。
Backgroundc-Jun NH2-terminal kinases (JNKs) are strongly activated by a stressful cellular environment, such as chemotherapy and oxidative stress. Autophagy is a protein-degradation system in which double-membrane vacuoles called autophagosomes are formed. The autophagy-related gene Beclin 1 plays a key role in this process. We previously found that autophagy was induced by dihydroartemisinin (DHA) in pancreatic cancer cells. However, little is known about the complex relationship between ROS, JNK activation, autophagy induction, and Beclin 1 expression.MethodsCell viability and CCK-8 assays were carried out to determine the cell proliferation; small interfering RNAs (siRNAs) were used to knockdown c-Jun NH2-terminal kinases (JNK1/2) genes; western blot was performed to detect the protein expression of LC3, JNK, Beclin 1, caspase 3 and β-actin; production of intracellular ROS was analyzed using FACS flow cytometry; autophagy induction was confirmed by electron microscopy.ResultsIn the present study, we explored the role of DHA and Beclin 1 expression in autophagy. DHA-treated cells showed autophagy characteristics, and DHA also activated the JNK pathway and up-regulated the expression of Beclin 1. Conversely, blocking JNK signaling inhibited Beclin 1 up-regulation. JNK activation was found to primarily depend on reactive oxygen species (ROS) resulting from the DHA treatment. Moreover, JNK pathway inhibition and Beclin 1 silencing prevented the induction of DHA-induced autophagy.ConclusionsThese results suggest that the induction of autophagy by DHA is required for JNK-mediated Beclin 1 expression.
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影响因子：
11.2
作者：
Apel, Anja;Herr, Ingrid;Mayer, Andreas
通讯作者：
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影响因子：
8
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
12.4
作者：
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通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
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