REGULATORY MECHANISM OF POLYUNSATURATED FATTY ACID IN THE PANCREATIC CANCER DEVELOPMENT

MAZO TAMARA; BRUNOTTO MABEL; FERRERO VICTORIA; FERNANDEZ ZAPICO MARTIN; GARAY ISABEL; BAROTTO NELSO; PASQUALINI MARIA EUGENIA

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Congreso; Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2021

Sociedad argentina de investigación bioquímica y biología molecular

Pancreatic ductal adenocarcinoma (PDCA) is one of the most aggressive and lethal cancers in the western world with a very poor survival. A characteristic pathway in the initiation of PDAC is the activation of the lipid-modified Sonic Hedgehog (SHH) ligand. Polyunsaturated fatty acids (PUFAs) are natural ligands of the transcription factor Gamma Peroxisome Proliferator Activated Receptor (PPARγ), which is also key to the SHH metabolic network. However, it is unknown how PUFAs regulate the SHH signaling pathway and PPARγ involved in the development of PDAC. Here we evaluated the effect of ω-3 and ω-6 PUFAs on SHH and PPARγ activation on tumor progression employing the human pancreatic cancer line PANC-1 in-vitro and in KPC knock-in transgenic mice in-vivo. PANC-1 cells were treated with PUFAs: arachidonic acid (ω-6, AA), eicosapentaenoic acid (ω-3, EPA) or docosahexaenoic acid (ω-3, DHA). Animals were fed with a semisynthetic diet with corn oil (ω-6) or fish oil (ω-3). The mRNA was analyzed by qPCR, proteins by Western Blot and cell viability of PANC-1 by Resazurin. Gas Chromatography was used to analyze the PUFAs profile of the PANC-1 cells and KPC mice tumors. Tumor volume was measured using a caliper, the fibrotic index by histologic assessment (Masson staining), the number of metastasis was counted on histological sections dyed with H-E and apoptotic cells, SHH and PPARγ by TUNEL and Immunohistochemistry techniques respectively. Data were analyzed by ANOVA. In PANC-1 cells the results showed that DHA reduced SHH gene and protein expression, increased PPARγ expression levels (p