title: Nrf2 promotes progression of non-small cell lung cancer through activating autophagy.
abstract: The transcription factor, NFE2-related factor 2 (Nrf2) and autophagy have been implicated in the oxidative-stress response during tumor evolution. However, few studies focus on crosstalk between Nrf2 and autophagy in cancer progression of non-small cell lung cancer (NSCLC). Herein, we evaluated the effect of Nrf2 on autophagy in NSCLC and their role in development of NSCLC. Effect of Nrf2 on overal survival (OS) of NSCLC patients were evaluated. Cell biological behaviors in response to Nrf2 were evaluated by MTT, colony formation assay and flow cytometry. Effect of 3-MA (a classical inhibitor of autophagy) on 95D-Nrf2 cells was also analyzed using flow cytometry. After up/down-regulating Nrf2 in NSCLC cell lines, expression of autophagy-related proteins were evaluated with western blot analysis. The results revealed that Nrf2 was an independent prognositc factor negtively associated with OS of NSCLC patients. Elevated Nrf2 expression promotes NSCLC progression, enhancing the escape of tumor cells from apoptosis in vivo and in vitro. Double staining with Annexin V-APC and 7-AAD showed that the proportions of apoptotic cells in 95D-Nrf2 cells were gradually increased after the addition of 3-MA. Importently, Nrf2 induced autophagosome formation and enhanced autophagic activity, which subsequently inhibits NSCLC cell apoptosis. In conclusion, our present study demonstrates that Nrf2 promotes progression of non-small cell lung cancer through activating autophagy. It provides novel insights into Nrf2-mediated of cell proliferation in NSCLC and may facilitate therapeutic development against NSCLC.
authors.affiliation: a Department of Oncology , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: a Department of Oncology , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , P. R. China.|b Department of Respiration, Department of Respiratory Medicine , Xi'an Central Hospital , Xi'an , Shaanxi Province , P. R. China.
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Liu
authors.affiliation: c Department of Respiration , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , P. R. China.
authors.forename: Tinghua
authors.initials: T
authors.lastname: Hu
authors.affiliation: d Department of Oncology , The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , P. R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Han
authors.affiliation: e Department of General Surgery , The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , P. R. China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Yu
authors.affiliation: a Department of Oncology , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: a Department of Oncology , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , P. R. China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Ruan
authors.affiliation: a Department of Oncology , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tian
authors.affiliation: a Department of Oncology , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , P. R. China.
authors.forename: Tianhe
authors.initials: T
authors.lastname: Huang
authors.affiliation: d Department of Oncology , The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , P. R. China.
authors.forename: Mincong
authors.initials: M
authors.lastname: Wang
authors.affiliation: a Department of Oncology , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Jing
authors.affiliation: a Department of Oncology , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , P. R. China.
authors.forename: Kejun
authors.initials: K
authors.lastname: Nan
authors.affiliation: a Department of Oncology , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi Province , P. R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D011379:Prognosis; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species
keywords: Nrf2; apoptosis; autophagy; cell proliferation; lung cancer