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GLUT5 增加了果糖的利用并促进了胶质瘤中的肿瘤进展。

GLUT5 increases fructose utilization and promotes tumor progression in glioma.

机构信息

Department of Neurosurgery, Jining NO.1 People's Hospital, Jining 272011, Shandong, China.

Department of Nursing, Jining Medical University, Jining 272011, Shandong, China.

出版信息

Biochem Biophys Res Commun. 2018 Jun 2;500(2):462-469. doi: 10.1016/j.bbrc.2018.04.103. Epub 2018 Apr 19.

Abstract

Fructose is now such an important component of human diets, and several studies have found that some cancer cells could utilize fructose to overcome low glucose micro-environment, but the study on the role of fructose in glioma is rare. To explore the role of fructose in glioma, we detected the proliferation and colony formation ability of glioma cells in fructose medium, and found that the abilities of proliferation and colony formation of glioma cells in fructose medium were similar with abilities in glucose medium, however, fructose just partly restored proliferation ability of normal glial cells. To explore the mechanism, we compared the expression level of GLUT5 (Glucose transporter type 5) in these cell lines, and the results showed that glioma cell lines had higher GLUT5 expression than normal glial cell lines. And knockdown of GLUT5 could significantly inhabit cell proliferation of glioma cells in fructose medium. Furthermore, we found that GLUT5 was also higher expressed in glioma tissues, and GLUT5 expression correlated significantly with glioma malignancy and poor survival of glioma patients (p < 0.01). In addition, we also demonstrated that knockdown of GLUT5 could significantly inhabit tumor proliferation in vivo, and intake fructose could increase tumor volume prominently. Taken together, our data show that fructose can be used by glioma cells, and restrict the fructose intake or targeting GLUT5 could be efficacious strategies in glioma.

摘要

果糖现在是人类饮食中非常重要的组成部分,有几项研究发现,一些癌细胞可以利用果糖来克服低糖微环境,但关于果糖在神经胶质瘤中作用的研究却很少。为了探讨果糖在神经胶质瘤中的作用,我们在果糖培养基中检测了神经胶质瘤细胞的增殖和集落形成能力,发现果糖培养基中神经胶质瘤细胞的增殖和集落形成能力与葡萄糖培养基中的能力相似,但果糖仅部分恢复了正常神经胶质细胞的增殖能力。为了探讨其机制,我们比较了这些细胞系中 GLUT5(葡萄糖转运蛋白 5)的表达水平,结果表明神经胶质瘤细胞系的 GLUT5 表达高于正常神经胶质细胞系。并且敲低 GLUT5 可显著抑制果糖培养基中神经胶质瘤细胞的增殖。此外,我们发现 GLUT5 在神经胶质瘤组织中也表达较高,并且 GLUT5 的表达与神经胶质瘤的恶性程度和神经胶质瘤患者的不良预后显著相关(p < 0.01)。此外,我们还证明了敲低 GLUT5 可显著抑制体内肿瘤的增殖,并且摄入果糖可显著增加肿瘤体积。总之,我们的数据表明,果糖可被神经胶质瘤细胞利用,限制果糖的摄入或靶向 GLUT5 可能是神经胶质瘤的有效治疗策略。

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