Statins Impair Glucose Uptake in Tumor Cells
Statins Impair Glucose Uptake in Tumor Cells
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DOI：
10.1593/neo.12444
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发表时间：
2012-04-01
期刊：
影响因子：
4.8
通讯作者：
Nowis, Dominika A.
中科院分区：
文献类型：
--
作者：
Malenda, Agata;Skrobanska, Anna;Nowis, Dominika A.
他汀类药物，HMG-CoA还原酶抑制剂，由于其降脂作用，被用于预防和治疗心血管疾病。既往研究表明，他汀类药物可通过调节膜胆固醇含量，诱导CD20聚类蛋白（cluster of differentiation 20, tetraspanin）构象改变。本研究的目的是研究他汀类药物对肿瘤细胞中葡萄糖转运蛋白1 （GLUT1）介导的葡萄糖摄取的影响。我们观察到他汀类药物培养的几种肿瘤细胞系中葡萄糖类似物的摄取显著的浓度和时间依赖性降低。用甲羟戊酸恢复胆固醇合成途径以及用外源性胆固醇补充质膜，这种作用是可逆的。他汀类药物在转录和蛋白水平上都没有改变GLUT1的总体表达。一项探索性临床试验显示，他汀类药物治疗降低了一套细胞淋巴瘤患者外周血白细胞的葡萄糖摄取，并降低了肿瘤肿块对f -18-氟脱氧葡萄糖（F-18-FDG）的摄取。生物信息学分析用于预测人类GLUT1的结构，并在其近膜片段中确定假定的胆固醇结合基序。总之，他汀类药物对葡萄糖摄取的影响似乎具有临床意义。通过抑制F-18-FDG的摄取，他汀类药物会对正电子发射断层扫描的敏感性产生负面影响，正电子发射断层扫描是肿瘤学中常用的诊断方法。
Statins, HMG-CoA reductase inhibitors, are used in the prevention and treatment of cardiovascular diseases owing to their lipid-lowering effects. Previous studies revealed that, by modulating membrane cholesterol content, statins could induce conformational changes in cluster of differentiation 20 (CD20) tetraspanin. The aim of the presented study was to investigate the influence of statins on glucose transporter 1 (GLUT1)- mediated glucose uptake in tumor cells. We observed a significant concentration- and time-dependent decrease in glucose analogs' uptake in several tumor cell lines incubated with statins. This effect was reversible with restitution of cholesterol synthesis pathway with mevalonic acid as well as with supplementation of plasma membrane with exogenous cholesterol. Statins did not change overall GLUT1 expression at neither transcriptional nor protein levels. An exploratory clinical trial revealed that statin treatment decreased glucose uptake in peripheral blood leukocytes and lowered F-18-fluorodeoxyglucose (F-18-FDG) uptake by tumor masses in a mantle cell lymphoma patient. A bioinformatics analysis was used to predict the structure of human GLUT1 and to identify putative cholesterol-binding motifs in its juxtamembrane fragment. Altogether, the influence of statins on glucose uptake seems to be of clinical significance. By inhibiting F-18-FDG uptake, statins can negatively affect the sensitivity of positron emission tomography, a diagnostic procedure frequently used in oncology.