Chen Xiangyuan, Wu Qichao, Sun Pengfei, Zhao Yanjun, Zhu Minmin, Miao Changhong
Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Anesthesiology, Fudan University Shanghai Medical College, Shanghai, China.
Cell Physiol Biochem. 2018;46(2):492-504. doi: 10.1159/000488617. Epub 2018 Mar 26.
BACKGROUND/AIMS: To investigate the effect of propofol on glucose metabolism in colorectal cancer cells and in an in vivo xenograft model.
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.
Propofol exposure induced a dose-dependent decrease of aerobic glycolysis in HT29 and SW480 colorectal cancer cells. MicroPET/CT indicated that propofol also inhibited 18F-FDG uptake in the xenograft model. In addition, hypoxia-inducible factor 1α (HIF1α) was also reduced by propofol dose-dependently. Propofol repressed the NMDAR-CAMKII-ERK pathway to inactivate HIF1α and therefore reduced glycolysis.
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.
背景/目的：研究丙泊酚对结肠癌细胞及体内异种移植模型中葡萄糖代谢的影响。
通过测量HT29和SW480结肠癌细胞的细胞外酸化率来评估葡萄糖代谢。分别采用定量实时聚合酶链反应和蛋白质免疫印迹分析检测mRNA和蛋白质水平。使用Fluo-3 AM荧光试剂盒评估细胞内钙。采用微型正电子发射断层扫描/计算机断层扫描（microPET/CT）成像分析异种移植模型肿瘤中的葡萄糖代谢。
丙泊酚暴露导致HT29和SW480结肠癌细胞中糖酵解呈剂量依赖性降低。MicroPET/CT表明丙泊酚在异种移植模型中也抑制了18F-FDG摄取。此外，丙泊酚还剂量依赖性地降低缺氧诱导因子1α（HIF1α）。丙泊酚抑制NMDAR-CAMKII-ERK途径使HIF1α失活，从而减少糖酵解。
丙泊酚通过使NMDAR-CAMKII-ERK途径失活来抑制结肠癌细胞中的有氧糖酵解，这可能有助于更好地理解丙泊酚在临床中的应用。
