title: Diabetes mellitus stimulates pancreatic cancer growth and epithelial-mesenchymal transition-mediated metastasis via a p38 MAPK pathway.
abstract: Diabetes mellitus (DM) and its accompanying chronic inflammation promote tumor progression. p38 mitogen-activated protein kinase (MAPK) is an essential kinase for inflammation. The effects of p38 MAPK on epithelial-mesenchymal transition (EMT)-mediated diabetic pancreatic cancer metastasis remain unclear. Here, we demonstrate that p38 MAPK phosphorylation was significantly increased in pancreatic cancer cells treated with high glucose and in pancreatic tumors from diabetic animals. A p38 MAPK inhibitor significantly suppressed the proliferation and invasion of pancreatic cancer cells under high-glucose conditions. Moreover, p38 MAPK inhibition not only significantly decreased both the tumor volume monitored by magnetic resonance imaging and EMT-related metastasis but also increased the survival of diabetic mice bearing pancreatic tumors. Furthermore, the inflammation in diabetic animals bearing pancreatic tumors was also significantly lower after therapy. Collectively, our findings reveal that p38 MAPK inhibitors may provide a novel intervention strategy for diabetic pancreatic cancer treatment.
authors.affiliation: Department of General Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Lishan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Bai
authors.affiliation: Department of General Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Hu
authors.affiliation: Department of General Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Zeqian
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Zhangjun
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of General Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Jiahua
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D048909:Diabetes Complications / Q000196:embryology* / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D010766:Phosphorylation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D048051:p38 Mitogen-Activated Protein Kinases
keywords: diabetes mellitus; epithelial-mesenchymal transition; inflammation; p38 MAPK; pancreatic cancer