PMID- 27986626
OWN - NLM
STAT- MEDLINE
DCOM- 20170508
LR  - 20180206
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 795
DP  - 2017 Jan 15
TI  - Propofol attenuates pancreatic cancer malignant potential via inhibition of NMDA 
      receptor.
PG  - 150-159
LID - S0014-2999(16)30786-5 [pii]
LID - 10.1016/j.ejphar.2016.12.017 [doi]
AB  - Propofol is a commonly used intravenous anesthetic, and could attenuate cancer 
      cells malignant potential via inhibiting hypoxia-inducible factor-1alpha (HIF-1alpha) 
      expression. However, the mechanism is still inclusive. In the present study, we 
      mainly focus on the mechanism by which propofol down-regulated HIF-1alpha 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-1alpha, phosphorylation of 
      extracellular regulated protein kinases (ERK), AKT, Ca(2+)/calmodulin dependent 
      protein kinases II (CaMK II), and Ca(2+) concentration in a 
      concentration-dependent manner (5, 25, 50, 100muM). 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.
CI  - Copyright (c) 2016 Elsevier B.V. All rights reserved.
FAU - Chen, Xiangyuan
AU  - Chen X
AD  - 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.
FAU - Wu, Qichao
AU  - Wu Q
AD  - 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.
FAU - You, Li
AU  - You L
AD  - Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Shanghai, 
      China.; Department of Oncology, Shanghai Medical College, Fudan University, 
      Shanghai, China.
FAU - Chen, Sisi
AU  - Chen S
AD  - Xuzhou Medical University, China.
FAU - Zhu, Minmin
AU  - Zhu M
AD  - 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.
FAU - Miao, Changhong
AU  - Miao C
AD  - 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.
LA  - eng
PT  - Journal Article
DEP - 20161213
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - SY7Q814VUP (Calcium)
RN  - YI7VU623SF (Propofol)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Mice
MH  - Pancreatic Neoplasms/metabolism/*pathology
MH  - Phosphorylation/drug effects
MH  - Propofol/*pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors
MH  - Vascular Endothelial Growth Factor A/metabolism
OTO - NOTNLM
OT  - CaMK II
OT  - HIF-1alpha
OT  - NMDA
OT  - Propofol
OT  - VEGF
EDAT- 2016/12/18 06:00
MHDA- 2017/05/10 06:00
CRDT- 2016/12/18 06:00
PHST- 2016/10/14 00:00 [received]
PHST- 2016/12/12 00:00 [revised]
PHST- 2016/12/12 00:00 [accepted]
PHST- 2016/12/18 06:00 [pubmed]
PHST- 2017/05/10 06:00 [medline]
PHST- 2016/12/18 06:00 [entrez]
AID - S0014-2999(16)30786-5 [pii]
AID - 10.1016/j.ejphar.2016.12.017 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2017 Jan 15;795:150-159. doi: 10.1016/j.ejphar.2016.12.017. Epub 
      2016 Dec 13.