RRC ID 43977
著者 Shimojo Y, Akimoto M, Hisanaga T, Tanaka T, Tajima Y, Honma Y, Takenaga K.
タイトル Attenuation of reactive oxygen species by antioxidants suppresses hypoxia-induced epithelial-mesenchymal transition and metastasis of pancreatic cancer cells.
ジャーナル Clin Exp Metastasis
Abstract Hypoxia has been shown to promote metastasis of cancer cells through induction of epithelial-mesenchymal transition (EMT). It is also known to cause generation of reactive oxygen species (ROS). We investigated here the role of ROS in hypoxia-induced EMT and whether attenuation of ROS by antioxidants suppresses hypoxia-induced EMT and metastasis of human pancreatic cancer cells in a xenograft nude mouse model. PANC-1 and MiaPaCa-2 cells exposed to hypoxia (1 % O(2)) showed increased ROS generation and characteristic changes of EMT such as morphological changes, enhanced invasiveness, and upregulation of EMT regulators, SLUG, SNAI1 and TWIST. The antioxidants N-acetylcysteine (NAC) and ebselen significantly suppressed EMT and the expression of EMT regulators during hypoxia. NAC abrogated activation of HIF-1α and NF-κB, both of which were found to play an active role in hypoxia-induced EMT. Administration of NAC to nude mice with orthotopic tumors suppressed the expression of EMT regulators in hypoxic areas and significantly inhibited hepatic metastasis. Together, the present findings demonstrate that attenuation of ROS by antioxidants suppresses hypoxia-induced EMT and metastatic phenotype, suggesting that antioxidants may be of therapeutic value in treating pancreatic cancers.
巻・号 30(2)
ページ 143-54
公開日 2013-2-1
DOI 10.1007/s10585-012-9519-8
PMID 22833345
MeSH Acetylcysteine / therapeutic use* Animals Antioxidants / therapeutic use* Apoptosis / drug effects Blotting, Western Cell Adhesion Cell Movement Cell Proliferation Epithelial-Mesenchymal Transition / drug effects* Female Fluorescent Antibody Technique Humans Hypoxia / pathology* Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors Hypoxia-Inducible Factor 1, alpha Subunit / genetics Hypoxia-Inducible Factor 1, alpha Subunit / metabolism Liver Neoplasms / metabolism Liver Neoplasms / prevention & control* Liver Neoplasms / secondary Mice Mice, Nude NF-kappa B / antagonists & inhibitors NF-kappa B / genetics NF-kappa B / metabolism Pancreatic Neoplasms / metabolism Pancreatic Neoplasms / pathology Pancreatic Neoplasms / prevention & control* RNA, Messenger / genetics RNA, Small Interfering / genetics Reactive Oxygen Species / metabolism* Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Snail Family Transcription Factors Transcription Factors / genetics Transcription Factors / metabolism Tumor Cells, Cultured Twist-Related Protein 1 / genetics Twist-Related Protein 1 / metabolism
IF 3.027
引用数 46
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 PANC-1(RCB2095) MIA Paca2(RCB2094)