DIETARY ω-3 POLYUNSATURATED FATTY ACIDS INHIBIT PANCREATIC CANCER PROGRESSION AND SHH SIGNALING IN A KPC MOUSE MODEL

FERRERO VICTORIA; GRANTON FLORENCIA; COMBA ANDREA; MARÍA EUGENIA PASQUALINI; MAZO TAMARA; LAGARES CLARISA; CREMONEZZI DAVID; FERNANDEZ ZAPICO MARTIN; GARAY ISABEL; BAROTTO NELSO N; MOREIRA- ESPINOZA MJ; BRUNOTTO MABEL

CORDOBA

Congreso; LX Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research (SAIB); 2024

Sociedad Argentina de Investigación en Bioquimica y Biologia Molecular

A significant number of cases of pancreatic cancer are due to modifiable risk factors such as fats consumed by the diet.Research studies suggest that diets high in omega-3 polyunsaturated fatty acids are associated with reduced pancreaticcancer risk. However, the scientific results appear insufficient for a general conclusion in pancreatic carcinogenesis.We investigated the effects of diet supplemented in fish oil high in ω-3 polyunsaturated fatty acids, the eicosapentaenoicacid (EPA, 20:5) and the docosahexaenoic acid (DHA, 22:6) and their derivatives the eicosanoids and their associationwith the ligand Sonic Hedgehog (SHH) and the peroxisome proliferator activator gamma receptors (PPARγ) onpancreatic cancer development in vivo. We used a transgenic mouse model that includes the knock-in of the G12Dmutant of KRAS activated by Cre recombinase in the exocrine pancreas and TP53-deficient (KPC mouse) mice fedwith semi-synthetic diets supplemented with 6% corn oil (control diet, high ω-6 PUFAs) or with 6% fish oil (high ω-3PUFAs). Our findings showed that dietary treatment with ω-3 PUFAs changed the tumor membrane fatty acid profile(Gas Chromatography), eicosanoids release (HPLC), and significantly reduced tumor volume, lung and liver metastasis(H-E stain) (p