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葡萄糖转运蛋白 1 活性抑制对神经母细胞瘤的体外影响。

Influence of glucose transporter 1 activity inhibition on neuroblastoma in vitro.

机构信息

Department of Physiology, Chongqing Medical University, Chongqing 400016, China; Department of Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China.

Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, China; Department of Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China.

出版信息

Gene. 2019 Mar 20;689:11-17. doi: 10.1016/j.gene.2018.12.010. Epub 2018 Dec 13.

Abstract

Most cancer cells predominantly produce their energy through a high rate of glycolysis in the presence of abundant oxygen. Glycolysis has become a target of anticancer strategies. Previous researches showed that glucose transporter 1 (GLUT1) inhibitor is effective as anticancer agents. This study assessed the effects of the selective GLUT1 inhibitor WZB117 on regulation of neuroblastoma (NB) cell line SH-SY5Y viability, cell cycle and glycolysis in vitro. SH-SY5Y cells were grown and treated with WZB117 for up to 72 h and then subjected to cell viability, qRT-PCR, Western blot and flow cytometry analysis. Level of ATP and LDH was also analyzed. The result showed that WZB117 treatment reduced tumor cells viability, downregulated level of GLUT1 protein. Moreover, WZB117 treatment arrested tumor cells at the G0-G1 phase of the cell cycle, induced tumor cells to undergo necrosis instead of apoptosis. In addition, WZB117 treatment downregulated the levels of intracellular ATP, LDH and glycolytic enzymes. Thus, WZB117-induced GLUT1 inhibition suppressed tumor cell growth, induced cell cycle arrest and reduced glycolysis metabolites in NB cells in vitro. This study suggested that GLUT1 can be used as a potential therapeutic target for NB.

摘要

大多数癌细胞在富含氧气的情况下主要通过高糖酵解率来产生能量。糖酵解已成为抗癌策略的目标。先前的研究表明,葡萄糖转运蛋白 1 (GLUT1) 抑制剂作为抗癌剂是有效的。本研究评估了选择性 GLUT1 抑制剂 WZB117 对体外神经母细胞瘤 (NB) 细胞系 SH-SY5Y 活力、细胞周期和糖酵解的调节作用。将 SH-SY5Y 细胞生长并用 WZB117 处理长达 72 小时,然后进行细胞活力、qRT-PCR、Western blot 和流式细胞术分析。还分析了 ATP 和 LDH 的水平。结果表明,WZB117 处理降低了肿瘤细胞活力,下调了 GLUT1 蛋白水平。此外,WZB117 处理将肿瘤细胞阻滞在细胞周期的 G0-G1 期,诱导肿瘤细胞发生坏死而不是凋亡。此外,WZB117 处理下调了细胞内 ATP、LDH 和糖酵解酶的水平。因此,WZB117 诱导的 GLUT1 抑制抑制了 NB 细胞的肿瘤细胞生长,诱导了细胞周期停滞,并减少了糖酵解代谢物。本研究表明,GLUT1 可作为 NB 的潜在治疗靶点。

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