Prevention of pancreatic acinar cell carcinoma by Roux-en-Y Gastric Bypass Surgery

• DOI: 10.1038/s41467-018-06571-w
• Publication Date: 2018-10-04T10:57:52Z
• Authors: Rui He; Yue Yin; Wenzhen Yin; Yin Li; Jing Zhao; Weizhen Zhang
• Keywords: 0301 basic medicine; Pancreatic Cancer Research and Treatment; Science; Gastric Bypass; Apoptosis; Nerve Tissue Proteins; Cancer research; Mechanistic Target of Rapamycin Complex 1; Signal transduction; Diet, High-Fat; Biochemistry; Article; Tuberous Sclerosis Complex 1 Protein; Metastasis; 03 medical and health sciences; Endocrinology; Biochemistry, Genetics and Molecular Biology; Health Sciences; Basic Helix-Loop-Helix Transcription Factors; Animals; Humans; Neoplasm Metastasis; Pancreatic Islet Dysfunction and Regeneration; Molecular Biology; Pancreas; mTORC1; Internal medicine; Biology; Cancer; Mice, Knockout; Carcinoma, Acinar Cell; Q; Body Weight; Gastroenterology; Life Sciences; Role of AMP-Activated Protein Kinase in Cellular Metabolism; Pancreatic cancer; Cancer Risk; 3. Good health; Pancreatic Neoplasms; Glucose; Oncology; PI3K/AKT/mTOR pathway; Medicine; Surgery; Energy Intake; Signal Transduction

AbstractRoux-en-Y Gastric Bypass Surgery (RYGB) prevents the occurrence of pancreatic cell acinar carcinoma (ACC) in male and female Ngn3-Tsc1−/− mice. Ngn3 directed Cre deletion of Tsc1 gene induced the development of pancreatic ACC. The transgenic mice with sham surgery demonstrated a cancer incidence of 96.7 ± 3.35% and survival rate of 67.0 ± 1.4% at the age of 300 days. Metastasis to liver and kidney was observed in 69.7 ± 9.7% and 44.3 ± 8.01% of these animals, respectively. All animals with RYGB performed at the age of 16 weeks survived free of pancreatic ACC up to the age of 300 days. RYGB significantly attenuated the activation of mTORC1 signaling and inhibition of tumor suppressor genes: p21, p27, and p53 in pancreatic ACC. Our studies demonstrate that bariatric surgery may limit the occurrence and growth of pancreatic ACC through the suppression of mTORC1 signaling in pancreas. RYGB shows promise for intervention of both metabolic dysfunction and organ cancer.