Abstract B51: Effects of dietary fatty acids on pancreatic cancer
Authors: Liu Hongyi , Yu Ming , Duan Yijie , Zhang Dapeng , Li Shasha , Chen Yue , Wang Feng 
Published: October 2015

Introduction: Fatty acids (FAs) are principal constituents of dietary fat. Epidemiological studies show that high fat diets (HFDs) regulate pancreatic cancer. However, the nature of the regulation may depend on the major types of dietary FAs namely saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) and n6- and n3 polyunsaturated fatty acids (n6PUFAs and n3PUFAs). We undertook the present study to investigate effects of these FAs on pancreatic cancer. Methods: We made four HFDs that all had 15% fat and 4 kcal/g. Fat contents in these HFDs were derived from cocoa butter, olive oil, soybean oil and flaxseed oil, respectively. These fat origins were chosen because in each of them more than 50% of total FAs are from a single FA type. Consequently, four HFDs were enriched with SFAs, MUFAs, n6PUFAs and n3PUFAs, respectively. Two normal-fat (4%-5%) diets were used as controls. One of them was iso-caloric to HFDs (IsoC control) and the other was normal chow (NC control, 3 kcal/g). The 6 diets were used in 6 groups of nude mice whose pancreas carried human pancreatic cancer cells. Fourteen weeks later, all mice were sacrificed. FA profiling was determined in liver and skeletal muscle by chromatography. Tumor grafts were analyzed by histology and Western blots. Results: The intake of HFDs that were rich in certain types of FAs increased the same types of FAs in the liver and skeletal muscle. The tumors whose hosts were fed MUFA diet were significantly greater than those whose hosts were fed NC, IsoC, and n3PUFA diets. The tumors whose hosts were fed SFA and n6PUFA diets were marginally greater than those in NC, IsoC, and n3PUFA groups. Necrotic areas were seen in all tumors. Big necrotic areas (&gt;25% of total tumor areas) were most frequent in the n3PUFA group, which suggests that n3PUFA diet promoted cancer-cell death. Medium-chain acyl-CoA dehydrogenase (MCAD) is known to regulate the beta-oxidation of FAs. When MCAD expression was determined by immunocytochemistry, the expression was more profound in tumors from SFA, MUFA, and n6PUFA groups than from NC, IsoC, and n3PUFA groups. When lipid droplets were stained in tumor sections, the droplets were scarce in control groups and were numerous in all HFD groups. When transcription factor hypoxia-inducible factor-1 (HIF-1) and proliferating cell nuclear antigen (PCNA) were stained by immunocytochemistry, a HIF-1/PCNA co-expression was seen in tumors from MUFA and n6PUFA groups. Previous studies have shown that cyclooxygenase-2 (COX-2) and superoxide dismutase-1 (SOD-1) may be involved in FA-induced regulation. Our Western blotting data suggest that COX-2 and SOD-1 were increased in tumors from four HFD groups, particularly SFA, MUFA, and n6PUFA groups. Conclusion: Pancreatic cancer cells are in a favorable condition when their hosts are fed diets rich in SFAs, MUFAs and n6PUFAs. In contrast, the diet rich in n3PUFAs has anticancer effects on pancreatic cancer cells.

Citation Format: Hongyi Liu, Ming Yu, Yijie Duan, Dapeng Zhang, Shasha Li, Yue Chen, Feng Wang. Effects of dietary fatty acids on pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B51.