4 325

Cited 54 times in

Omega-3-polyunsaturated fatty acids suppress pancreatic cancer cell growth in vitro and in vivo via downregulation of Wnt/Beta-catenin signaling

Authors
 Kyoung-Sub Song  ;  Kaipeng Jing  ;  Jong-Seok Kim  ;  Eun-Jin Yun  ;  Soyeon Shin  ;  Kang-Sik Seo  ;  Ji-Hoon Park  ;  Jun-Young Heo  ;  Jing X. Kang  ;  Kwang-Sun Suh  ;  Tong Wu  ;  Jong-Il Park  ;  Gi-Ryang Kweon  ;  Wan-Hee Yoon  ;  Byung-Doo Hwang  ;  Kyu Lim 
Citation
 PANCREATOLOGY, Vol.11(6) : 574-584, 2011 
Journal Title
 PANCREATOLOGY 
ISSN
 1424-3903 
Issue Date
2011
MeSH
Adenocarcinoma/drug therapy* ; Adenocarcinoma/genetics ; Adenocarcinoma/pathology ; Animals ; Antineoplastic Agents/pharmacology* ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Docosahexaenoic Acids/pharmacology* ; Down-Regulation/drug effects ; Drug Screening Assays, Antitumor ; Eicosapentaenoic Acid/pharmacology* ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mice ; Mice, Transgenic ; Pancreatic Neoplasms/drug therapy* ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; Wnt Signaling Pathway/drug effects* ; Wnt Signaling Pathway/genetics
Keywords
ω3-PUFAs ; Pancreatic cancer ; Wnt/β-catenin ; Apoptosis
Abstract
BACKGROUND/AIMS: ω3-polyunsaturated fatty acids (ω3- PUFAs) are known to possess anticancer properties. However, the relationship between ω3-PUFAs and β-catenin, one of the key components of the Wnt signaling pathway, in human pancreatic cancer remains poorly characterized. METHODS: Human pancreatic cancer cells (SW1990 and PANC-1) were exposed to two ω3-PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), to investigate the relationship between ω3-PUFAs and the Wnt/β-catenin signaling pathway in vitro. Mouse pancreatic cancer (PANC02) cells were implanted into fat-1 transgenic mice, which express ω3 desaturases and result in elevated levels of ω3-PUFAs endogenously. The tumor size, levels of Wnt/β-catenin signaling molecules and apoptosis levels were analyzed to examine the influence of ω3-PUFAs in vivo. RESULTS: DHA and EPA significantly inhibited cell growth and increased cell death in pancreatic cancer cells. DHA also reduced β-catenin expression, T cell factor/lymphoid-enhancing factor reporter activity and induced β-catenin/Axin/GSK-3β complex formation, a known precursor to β-catenin degradation. Furthermore, Wnt3a, a natural canonical Wnt pathway ligand, reversed DHA-induced growth inhibition in PANC-1 cells. Immunohistochemical analysis showed aberrant upregulation and increased nuclear staining of β-catenin in tumor tissues from pancreatic cancer patients. However, β-catenin levels in tumor tissues from fat-1 transgenic mice were reduced with a significant increase in apoptosis compared with those from control mice. CONCLUSION: ω3-PUFAs may be an effective therapy for the chemoprevention and treatment of human pancreatic cancer. and IAP.
Full Text
http://www.sciencedirect.com/science/article/pii/S1424390311801109
DOI
10.1159/000334468
Appears in Collections:
5. Research Institutes (연구소) > Institute for Immunology and Immunological Disease (면역질환연구소) > 1. Journal Papers
Yonsei Authors
Kim, Jong Seok(김종석)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/95468
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse