The Relevance of Nrf2 Pathway and Autophagy in Pancreatic Cancer Cells upon Stimulation of Reactive Oxygen Species.
The Relevance of Nrf2 Pathway and Autophagy in Pancreatic Cancer Cells upon Stimulation of Reactive Oxygen Species.
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活性氧刺激下胰腺癌细胞中 Nrf2 通路与自噬的相关性
DOI：
10.1155/2016/3897250
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发表时间：
2016
影响因子：
--
通讯作者：
Shen X
中科院分区：
文献类型：
--
作者：
Zhang L;Li J;Ma J;Chen X;Chen K;Jiang Z;Zong L;Yu S;Li X;Xu Q;Lei J;Duan W;Li W;Shan T;Ma Q;Shen X
Nrf 2（NF-E2-related factor 2）通路和自噬都能响应氧化应激，促进癌细胞在肿瘤微环境中存活。因此，我们探讨了Nrf 2通路与胰腺癌细胞在活性氧（ROS）刺激下自噬的相关性。胰腺癌细胞在受控的ROS应激条件或基础条件下培养。不同的抑制剂用于防止特定阶段的自噬。Nrf 2 siRNA用于抑制Nrf 2通路活化。Ad-mRFP-GFP-LC 3感染用于监测自噬通量。结果表明，少量外源性过氧化氢（H2 O2）可显著提高细胞内ROS水平。此外，我们的研究结果表明，ROS促进胰腺癌细胞中Nrf 2通路和自噬的激活。此外，我们的数据表明，在特定阶段抑制自噬活性导致ROS刺激后Nrf 2通路活化的促进增加。此外，我们发现Nrf 2的沉默促进ROS刺激后的自噬。此外，Nrf 2干扰有效地促进ROS刺激后的自噬通量。总之，我们的研究结果表明，Nrf 2途径和自噬有一个负相互作用，在ROS刺激。
Nrf2 (NF-E2-related factor 2) pathway and autophagy both can respond to oxidative stress to promote cancer cells to survive in the tumor microenvironment. We, therefore, explored the relevance between Nrf2 pathway and autophagy in pancreatic cancer cells upon stimulation of reactive oxygen species (ROS). Pancreatic cancer cells were cultured under controlled ROS stressing condition or basal condition. Different inhibitors were used to prevent autophagy at particular stages. Nrf2 siRNA was used to inhibit Nrf2 pathway activation. Ad-mRFP-GFP-LC3 infection was used to monitor autophagic flux. The result shows that a small amount of exogenous hydrogen peroxide (H2O2) can significantly improve the level of intracellular ROS. Moreover, our findings indicate that ROS promotes the activation of both Nrf2 pathway and autophagy in pancreatic cancer cells. Moreover, our data demonstrate that suppression of autophagic activity at particular stages results in an increased promotion of Nrf2 pathway activation upon ROS stimulation. Furthermore, we found that silencing of Nrf2 promotes autophagy upon ROS stimulation. In addition, Nrf2 interference effectively promotes autophagic flux upon ROS stimulation. In summary, our findings suggest that Nrf2 pathway and autophagy have a negative interaction with each other upon ROS stimulation.