title: The Relevance of Nrf2 Pathway and Autophagy in Pancreatic Cancer Cells upon Stimulation of Reactive Oxygen Species.
abstract: 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.
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Lun
authors.identifier: 0000-0003-1936-3971
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Jiahui
authors.identifier: 0000-0003-1845-9234
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Jiguang
authors.identifier: 0000-0002-7296-2554
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Xin
authors.identifier: 0000-0003-0509-7510
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Ke
authors.identifier: 0000-0003-3148-9921
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Zhengdong
authors.identifier: 0000-0003-0234-5478
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Liang
authors.identifier: 0000-0002-3330-4735
authors.initials: L
authors.lastname: Zong
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
authors.forename: Shuo
authors.identifier: 0000-0002-4082-2581
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Xuqi
authors.identifier: 0000-0002-2497-020X
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Qinhong
authors.identifier: 0000-0003-0654-5290
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Jianjun
authors.identifier: 0000-0001-8258-705X
authors.initials: J
authors.lastname: Lei
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Wanxing
authors.identifier: 0000-0002-2851-2513
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Wei
authors.identifier: 0000-0001-5701-3230
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
authors.forename: Tao
authors.identifier: 0000-0001-6680-9302
authors.initials: T
authors.lastname: Shan
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Qingyong
authors.identifier: 0000-0001-8977-320X
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Xin
authors.identifier: 0000-0003-4255-5883
authors.initials: X
authors.lastname: Shen
mesh_terms: D001343:Autophagy; D045744:Cell Line, Tumor; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species