title: Superoxide dismutase promotes the epithelial-mesenchymal transition of pancreatic cancer cells via activation of the H2O2/ERK/NF-κB axis.
abstract: Our previous study revealed that superoxide dismutase (SOD)-dependent production of reactive oxygen species (ROS) was able to increase the invasive ability of pancreatic cancer cells. However, the underlying mechanisms by which SOD enhances metastasis are still not fully elucidated. As epithelial-mesenchymal transition (EMT) is a key player in tumor metastasis, the aim of this study was to evaluate whether SOD affects EMT in pancreatic cancer cells and the related mechanism. Human pancreatic cancer cells BxPC-3 and Panc-1 were utilized to examine the level of hydrogen peroxide (H2O) in the absence or presence of SOD and catalase (CAT). The activation of phospho-ERK and phospho-NF-κB were measured by western blot analysis. Wound healing assay and transwell invasion assay were used to detect the migratory and invasive potential of cancer cells. The EMT-related factors, E-cadherin, N-cadherin and vimentin were detected by QT-PCR and western blot analysis. The results of present study showed that SOD not only increased cell migration and invasion in pancreatic cancer, but also mediated the expression of EMT-related factors and cell morphology. In addition, the levels of phospho-ERK and phospho-NF-κB were induced by SOD which could be counter-balanced by both CAT treatment and PD 98059 (an ERK inhibitor). Taken together, these data indicate that SOD promotes the invasive and migratory activity of pancreatic cancer. Blocking the H2O2/ERK/NF-κB axis might be a novel strategy for the treatment of this severe malignancy.
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Qinhong
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, P.R. China.
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Ma
mesh_terms: D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D010766:Phosphorylation; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: D005419:Flavonoids; D016328:NF-kappa B; C000606290:SOD1 protein, human; D006861:Hydrogen Peroxide; C577219:CAT protein, human; D002374:Catalase; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one