Increased lipid metabolism and cell turnover of MiaPaCa2 cells induced by high-fat diet in an orthotopic system.

In this study, we investigated whether increased dietary fat influences established pancreatic cancer cells. MiaPaCa2 human pancreatic cancer cells were grown orthotopically in athymic mice fed normal diet (ND) or high-fat diet (HF). In the resulting tumors, medium-chain acyl-coenzyme A dehydrogenase (MCAD, a regulator of fatty acid beta-oxidation) and Cu/Zn-superoxide dismutase (an antioxidant enzyme) were determined using Western blotting. The MCAD messenger RNA (mRNA) was determined by real-time polymerase chain reaction. Intracellular lipid droplets, proliferating cells (Ki67 positive), and apoptotic cells were stained in tumor sections. The HF tumors were heavier than the ND tumors (1.60 +/- 0.08 vs 1.13 +/- 0.10 g, P < .01, 6 tumors per group). The MCAD and Cu/Zn-superoxide dismutase proteins and the MCAD mRNA were increased in HF tumors compared with those seen in ND tumors. The HF tumors contained extensive central necrosis, which was surrounded with apoptotic and proliferating cells. The HF tumors also showed numerous lipid droplets. In the ND tumors, necrosis was uncommon, apoptotic cells were sporadic, and lipid droplets were few. In follow-up experiments, MiaPaCa2 cells were incubated in vitro in the presence or absence of fatty acids (oleic and linoleic acids). The fatty acid exposure increased lipid droplets, cell proliferation, and MCAD mRNA expression in MiaPaCa2 cells. In conclusion, increased dietary fat stimulates lipid metabolism and cell turnover in MiaPaCa2 human pancreatic cancer cells.