Propofol attenuates the adhesion of tumor and endothelial cells through inhibiting glycolysis in human umbilical vein endothelial cells

<title>Abstract</title>Propofol is one of the most commonly used intravenous anesthetics and plays an important role in tumor suppression. In the present study, we aimed to investigate the mechanism by which propofol attenuates tumor endothelial cells (TECs) and tumor cell adhesion to in...

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Main Authors: Qi Jie, Wu Qichao, Zhu Xuqin, Zhang Shan, Chen Xiangyuan, Chen Wankun, Sun Zhirong, Zhu Minmin, Miao Changhong
Format: Article
Language:English
Published: China Science Publishing & Media Ltd. 2019-10-01
Series:Acta Biochimica et Biophysica Sinica
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Online Access:https://www.sciengine.com/doi/10.1093/abbs/gmz105
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author Qi Jie
Wu Qichao
Zhu Xuqin
Zhang Shan
Chen Xiangyuan
Chen Wankun
Sun Zhirong
Zhu Minmin
Miao Changhong
author_facet Qi Jie
Wu Qichao
Zhu Xuqin
Zhang Shan
Chen Xiangyuan
Chen Wankun
Sun Zhirong
Zhu Minmin
Miao Changhong
author_sort Qi Jie
collection DOAJ
description <title>Abstract</title>Propofol is one of the most commonly used intravenous anesthetics and plays an important role in tumor suppression. In the present study, we aimed to investigate the mechanism by which propofol attenuates tumor endothelial cells (TECs) and tumor cell adhesion to inhibit tumor metastasis in vitro. Human umbilical vein endothelial cells (HUVECs) cultured in Dulbecco’s modified Eagle’s medium were treated with tumor conditioned medium for 24 h, followed by 4 h of treatment with or without 25 μM of propofol, 10 μM of KN93, 500 μM of MK801, or 20 μM of rapastinel. It was found that propofol inhibited TEC adhesion and the glycolysis level of TECs. Consistently, propofol inhibited the expressions of adhesion molecules (E-selectin, ICAM-1, and VCAM-1) and glycolysis proteins (GLUT1, HK2, and LDHA) in TECs. Moreover, propofol attenuated the expression of HIF-1α, the phosphorylation of AKT and Ca<sup>2+</sup>/calmodulin-dependent protein kinase II (CaMKII), and the Ca<sup>2+</sup> concentration in TECs. MK801, an inhibitor of NMDA receptor, and KN93, an inhibitor of CaMKII, both inhibited the expressions of adhesion molecules and glycolysis proteins, in a manner similar to propofol. Additionally, rapastine, an activator of NMDA receptor, could counteract the effects of propofol. Our results indicated that propofol attenuates intracellular Ca<sup>2+</sup> concentration, CaMKII and AKT phosphorylation, and HIF-1α expression, probably via inhibiting the NMDA receptor, thus inhibiting glycolysis and adhesion of tumor and endothelial cells.
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spelling doaj-art-e795c6c88ddf4855a69eaddd00c9e7ec2025-08-20T01:52:21ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452019-10-01511114112210.1093/abbs/gmz10520d259ccPropofol attenuates the adhesion of tumor and endothelial cells through inhibiting glycolysis in human umbilical vein endothelial cellsQi Jie0Wu Qichao1Zhu Xuqin2Zhang Shan3Chen Xiangyuan4Chen Wankun5Sun Zhirong6Zhu Minmin7Miao Changhong8["Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China","Department of Anaesthesiology, Shanghai Medical College, Fudan University, Shanghai 200032, China"]["Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China","Department of Anaesthesiology, Shanghai Medical College, Fudan University, Shanghai 200032, China"]["Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China"]["Department of Anaesthesia, Critical Care and Pain Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China"]["Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China","Department of Anaesthesiology, Shanghai Medical College, Fudan University, Shanghai 200032, China"]["Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China"]["Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China"]["Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China"]["Department of Anaesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China"]<title>Abstract</title>Propofol is one of the most commonly used intravenous anesthetics and plays an important role in tumor suppression. In the present study, we aimed to investigate the mechanism by which propofol attenuates tumor endothelial cells (TECs) and tumor cell adhesion to inhibit tumor metastasis in vitro. Human umbilical vein endothelial cells (HUVECs) cultured in Dulbecco’s modified Eagle’s medium were treated with tumor conditioned medium for 24 h, followed by 4 h of treatment with or without 25 μM of propofol, 10 μM of KN93, 500 μM of MK801, or 20 μM of rapastinel. It was found that propofol inhibited TEC adhesion and the glycolysis level of TECs. Consistently, propofol inhibited the expressions of adhesion molecules (E-selectin, ICAM-1, and VCAM-1) and glycolysis proteins (GLUT1, HK2, and LDHA) in TECs. Moreover, propofol attenuated the expression of HIF-1α, the phosphorylation of AKT and Ca<sup>2+</sup>/calmodulin-dependent protein kinase II (CaMKII), and the Ca<sup>2+</sup> concentration in TECs. MK801, an inhibitor of NMDA receptor, and KN93, an inhibitor of CaMKII, both inhibited the expressions of adhesion molecules and glycolysis proteins, in a manner similar to propofol. Additionally, rapastine, an activator of NMDA receptor, could counteract the effects of propofol. Our results indicated that propofol attenuates intracellular Ca<sup>2+</sup> concentration, CaMKII and AKT phosphorylation, and HIF-1α expression, probably via inhibiting the NMDA receptor, thus inhibiting glycolysis and adhesion of tumor and endothelial cells.https://www.sciengine.com/doi/10.1093/abbs/gmz105propofoltumor endothelial cellglycolysisHIF-1αCaMKII
spellingShingle Qi Jie
Wu Qichao
Zhu Xuqin
Zhang Shan
Chen Xiangyuan
Chen Wankun
Sun Zhirong
Zhu Minmin
Miao Changhong
Propofol attenuates the adhesion of tumor and endothelial cells through inhibiting glycolysis in human umbilical vein endothelial cells
Acta Biochimica et Biophysica Sinica
propofol
tumor endothelial cell
glycolysis
HIF-1α
CaMKII
title Propofol attenuates the adhesion of tumor and endothelial cells through inhibiting glycolysis in human umbilical vein endothelial cells
title_full Propofol attenuates the adhesion of tumor and endothelial cells through inhibiting glycolysis in human umbilical vein endothelial cells
title_fullStr Propofol attenuates the adhesion of tumor and endothelial cells through inhibiting glycolysis in human umbilical vein endothelial cells
title_full_unstemmed Propofol attenuates the adhesion of tumor and endothelial cells through inhibiting glycolysis in human umbilical vein endothelial cells
title_short Propofol attenuates the adhesion of tumor and endothelial cells through inhibiting glycolysis in human umbilical vein endothelial cells
title_sort propofol attenuates the adhesion of tumor and endothelial cells through inhibiting glycolysis in human umbilical vein endothelial cells
topic propofol
tumor endothelial cell
glycolysis
HIF-1α
CaMKII
url https://www.sciengine.com/doi/10.1093/abbs/gmz105
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