Omega-3 Fatty Acids Prevent Early Pancreatic Carcinogenesis via Repression of the AKT Pathway

Nutrients

Michel Ouellette¹  Michelle Schultz²  Michael Heiferman²  Yongzeng Ding²  Mireille Wojtanek²  Emman Mascariñas²  Brian DeCant²  Morgan Barron²  DavidJ. Bentrem²  Bhargava Mullapudi²  PaulJ. Grippo²  Kevin Adrian²  Carolina Torres³  Georgina Mancinelli³  AndrewM. Diaz³  Sambasiva Rao³  Ronald McKinney³  Ming-Sound Tsao⁴ 

[1]Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA

[2]Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA

[3]Division of Gastroenterology, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA

[4]Toronto General Hospital, 200 Elizabeth St., Toronto, ON M5G 2C4, Canada

关键词: pancreatic cancer;    chemoprevention;    neoplastic disease;    proliferation;    polyunsaturated fatty acids;   

DOI  :  10.3390/nu10091289

来源: DOAJ

【 摘 要 】

Pancreatic cancer remains a daunting foe despite a vast number of accumulating molecular analyses regarding the mutation and expression status of a variety of genes. Indeed, most pancreatic cancer cases uniformly present with a mutation in the KRAS allele leading to enhanced RAS activation. Yet our understanding of the many epigenetic/environmental factors contributing to disease incidence and progression is waning. Epidemiologic data suggest that diet may be a key factor in pancreatic cancer development and potentially a means of chemoprevention at earlier stages. While diets high in ω3 fatty acids are typically associated with tumor suppression, diets high in ω6 fatty acids have been linked to increased tumor development. Thus, to better understand the contribution of these polyunsaturated fatty acids to pancreatic carcinogenesis, we modeled early stage disease by targeting mutant KRAS to the exocrine pancreas and administered diets rich in these fatty acids to assess tumor formation and altered cell-signaling pathways. We discovered that, consistent with previous reports, the ω3-enriched diet led to reduced lesion penetrance via repression of proliferation associated with reduced phosphorylated AKT (pAKT), whereas the ω6-enriched diet accelerated tumor formation. These data provide a plausible mechanism underlying previously observed effects of fatty acids and suggest that administration of ω3 fatty acids can reduce the pro-survival, pro-growth functions of pAKT. Indeed, counseling subjects at risk to increase their intake of foods containing higher amounts of ω3 fatty acids could aid in the prevention of pancreatic cancer.

【 授权许可】

Unknown