Omega-3-Polyunsaturated Fatty Acids Suppress Pancreatic Cancer Cell Growth in vitro and in vivo via Downregulation of Wnt/Beta-Catenin Signaling

Background/Aims: omega 3-polyunsaturated fatty acids (omega 3-PUFAs) are known to possess anticancer properties. However, the relationship between omega 3-PUFAs and beta-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 omega 3-PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), to investigate the relationship between omega 3-PUFAs and the Wnt/beta-catenin signaling pathway in vitro. Mouse pancreatic cancer (PANC02) cells were implanted into fat-1 transgenic mice, which express omega 3 desaturases and result in elevated levels of omega 3-PUFAs endogenously. The tumor size, levels of Wnt/beta-catenin signaling molecules and apoptosis levels were analyzed to examine the influence of omega 3-PUFAs in vivo. Results: DHA and EPA significantly inhibited cell growth and increased cell death in pancreatic cancer cells. DHA also reduced beta-catenin expression, T cell factor/lymphoid-enhancing factor reporter activity and induced beta-catenin/Axin/GSK-3 beta complex formation, a known precursor to beta-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 beta-catenin in tumor tissues from pancreatic cancer patients. However, beta-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: omega 3-PUFAs may be an effective therapy for the chemoprevention and treatment of human pancreatic cancer. Copyright (C) 2011 S. Karger AG, Basel and IAP