Propofol Disrupts Aerobic Glycolysis in Colorectal Cancer Cells via Inactivation of the NMDAR-CAMKII-ERK Pathway
Propofol Disrupts Aerobic Glycolysis in Colorectal Cancer Cells via Inactivation of the NMDAR-CAMKII-ERK Pathway
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DOI：
10.1159/000488617
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Miao, Changhong
中科院分区：
文献类型：
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作者：
Chen, Xiangyuan;Wu, Qichao;Miao, Changhong
背景/目的：研究异丙酚对结直肠癌细胞和体内异种移植模型中糖代谢的影响。方法：通过测定HT29和SW480结直肠癌细胞的胞外酸化率来评价葡萄糖代谢。定量实时定量聚合酶链式反应和蛋白质印迹分析分别检测mRNA和蛋白质水平。用Fluo-3AM荧光试剂盒检测细胞内钙离子浓度。用微正电子发射断层扫描/计算机断层扫描(microPET/CT)成像技术分析移植瘤中的糖代谢。结果：异丙酚诱导HT29和SW480结直肠癌细胞有氧酵解作用呈剂量依赖性减少。MicroPET/CT显示异丙酚还抑制异种移植模型中8F-FDG的摄取。此外，异丙酚还剂量依赖性地减少缺氧诱导因子1a(HIF1a)。异丙酚抑制NMDAR-CaMKII-ERK途径使HIF1a失活，从而减少糖酵解。结论：异丙酚通过灭活NMDAR-CaMKII-ERK途径抑制结直肠癌细胞的有氧糖酵解，这可能有助于更好地理解异丙酚在临床上的使用。(C)2018年作者S(S)在巴塞尔卡格尔出版
Background/Aims: To investigate the effect of propofol on glucose metabolism in colorectal cancer cells and in an in vivo xenograft model. Methods: Glucose metabolism was assessed by measuring the extracellular acidification rate in HT29 and SW480 colorectal cancer cells. Quantitative real-time PCR and western blot analyses were used to detect mRNA and protein levels, respectively. Intracellular calcium was assessed by using a Fluo-3 AM fluorescence kit. Micro-positron emission tomography/computed tomography (microPET/CT) imaging was used to analyze glucose metabolism in the tumors of the xenograft model. Results: Propofol exposure induced a dose-dependent decrease of aerobic glycolysis in HT29 and SW480 colorectal cancer cells. MicroPET/CT indicated that propofol also inhibited '8F-FDG uptake in the xenograft model. In addition, hypoxia-inducible factor la (HIF1a) was also reduced by propofol dose-dependently. Propofol repressed the NMDAR-CAMKII-ERK pathway to inactivate HIFla and therefore reduced glycolysis. Conclusion: Propofol inhibited aerobic glycolysis in colorectal cancer cells through the inactivation of the NMDAR-CAMKII-ERK pathway, which may facilitate a better understanding of the use of propofol in the clinical setting. (C) 2018 The Author(s) Published by S Karger AG, Basel