Omega-3-polyunsaturated fatty acids suppress pancreatic cancer cell growth in vitro and in vivo via downregulation of Wnt/Beta-catenin signaling.
Pancreatology
; 11(6): 574-84, 2011.
Article
en En
| MEDLINE
| ID: mdl-22213040
ABSTRACT
BACKGROUND/AIMS:
ω3-polyunsaturated fatty acids (ω3- PUFAs) are known to possess anticancer properties. However, the relationship between ω3-PUFAs and ß-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/ß-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/ß-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 ß-catenin expression, T cell factor/lymphoid-enhancing factor reporter activity and induced ß-catenin/Axin/GSK-3ß complex formation, a known precursor to ß-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 ß-catenin in tumor tissues from pancreatic cancer patients. However, ß-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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
/
Adenocarcinoma
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Ácido Eicosapentaenoico
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Ácidos Docosahexaenoicos
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Vía de Señalización Wnt
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Antineoplásicos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Pancreatology
Asunto de la revista:
ENDOCRINOLOGIA
/
GASTROENTEROLOGIA
Año:
2011
Tipo del documento:
Article