title: Propofol attenuates pancreatic cancer malignant potential via inhibition of NMDA receptor.
abstract: Propofol is a commonly used intravenous anesthetic, and could attenuate cancer cells malignant potential via inhibiting hypoxia-inducible factor-1α (HIF-1α) expression. However, the mechanism is still inclusive. In the present study, we mainly focus on the mechanism by which propofol down-regulated HIF-1α expression and malignant potential in pancreatic cancer cells. Human pancreatic cancer cells (Miapaca-2 and Panc-1) in vitro and murine pancreatic cancer cell (Panc02) in vivo were used to assess the effect of propofol on vascular endothelial growth factor (VEGF) expression and migration of pancreatic cancer cells. Propofol inhibited cells migration, expression of VEGF and HIF-1α, phosphorylation of extracellular regulated protein kinases (ERK), AKT, Ca2+/calmodulin dependent protein kinases II (CaMK II), and Ca2+concentration in a concentration-dependent manner (5, 25, 50, 100μM). Furthermore, MK801, an inhibitor of NMDA receptor, and KN93, an inhibitor of CaMK II, could inhibit the expression of VEGF, HIF-1a, p-AKT, p-ERK, p-CaMK II in vitro, growth of tumor and VEGF expression in vivo, which were similar to the effect of propofol. In addition, the anti-tumor effect of propofol could be counteracted by rapastinel, an activator of NMDA receptor. Our study indicated that propofol suppressed VEGF expression and migration ability of pancreatic cancer cells in vitro and in vivo, probably via inhibiting NMDA receptor.
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Anesthesiology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Xiangyuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Anesthesiology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Qichao
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: You
authors.affiliation: Xuzhou Medical University, China.
authors.forename: Sisi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: zhu_mm@126.com.
authors.forename: Minmin
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: miao_chh@126.com.
authors.forename: Changhong
authors.initials: C
authors.lastname: Miao
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D051379:Mice; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016194:Receptors, N-Methyl-D-Aspartate; D042461:Vascular Endothelial Growth Factor A; D051057:Proto-Oncogene Proteins c-akt; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium; D015742:Propofol
keywords: CaMK II; HIF-1α; NMDA; Propofol; VEGF