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肿瘤细胞对荧光脱氧葡萄糖类似物(2-NBDG)的摄取。

Uptake of a fluorescent deoxyglucose analog (2-NBDG) in tumor cells.

作者信息

O'Neil Roger G, Wu Ling, Mullani Nizar

机构信息

Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, 6431 Fannin, Houston, TX 77030, USA.

出版信息

Mol Imaging Biol. 2005 Nov-Dec;7(6):388-92. doi: 10.1007/s11307-005-0011-6.

Abstract

PURPOSE

A new fluorescent analog of D -glucose was recently developed by [Yoshioka K, Takahashi H, Homma T, Sato M, Ki Bong O, Nemoto Y, Matsuoka H (1996) A novel fluorescent derivative of glucose applicable to the assessment of glucose uptake activity of Escherichia coli. Biochim Biophys Acta 1289:5-9] and shown to be transported into normal cells. The purpose of this preliminary study was to assess the use of this fluorescent 2-deoxyglucose analog, 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG), as a sensitive probe for monitoring glucose uptake into malignant tumor cells.

PROCEDURES

MCF-7 breast cancer epithelial cells were grown and plated on coverslips for analysis of 2-NBDG uptake via fluorescence imaging microscopy.

RESULTS

Steady-state fluorescence analysis of 2-NBDG uptake displayed rapid uptake for the first one to five minutes, then slowed, reaching an apparent maximum uptake near 20-30 minutes. Addition of 5 mM D -glucose to the media markedly reduced 2-NBDG uptake. Uptake of 2-NBDG in nonmalignant epithelial cells (M-1 epithelial cells) was slow, averaging less than 20% of that observed for tumorigenic cells, the MCF-7 breast cancer cells and the HepG2 liver cancer cell line.

CONCLUSIONS

The preliminary data clearly demonstrate a rapid uptake of 2-NBDG into tumor cells that can be monitored by fluorescence imaging analysis. The uptake displays saturation and competition with D -glucose, all properties expected for 2-NBDG uptake and retention in cancer cells. Additional studies, including comparisons among other malignant cell lines and control cells, will be needed to fully characterize the kinetic properties of 2-NBDG uptake and the potential use of this 2-DG analog as a probe for glucose uptake in malignant cells.

摘要

目的

[吉冈K、高桥H、本间T、佐藤M、基邦O、根本Y、松冈H(1996年)一种适用于评估大肠杆菌葡萄糖摄取活性的新型葡萄糖荧光衍生物。生物化学与生物物理学报1289:5 - 9]最近开发了一种新的D -葡萄糖荧光类似物,并证明其可转运至正常细胞中。本初步研究的目的是评估这种荧光2 -脱氧葡萄糖类似物2 - [N -(7 -硝基苯并 - 2 -恶唑 - 1,3 -二氮杂环戊烯 - 4 -基)氨基] - 2 -脱氧葡萄糖(2 - NBDG)作为监测恶性肿瘤细胞摄取葡萄糖的敏感探针的用途。

程序

培养MCF - 7乳腺癌上皮细胞并接种于盖玻片上,通过荧光成像显微镜分析2 - NBDG摄取情况。

结果

对2 - NBDG摄取的稳态荧光分析显示,最初1至5分钟摄取迅速,随后减慢,在20 - 30分钟左右达到明显的最大摄取量。向培养基中添加5 mM D -葡萄糖可显著降低2 - NBDG摄取。非恶性上皮细胞(M - 1上皮细胞)对2 - NBDG的摄取缓慢,平均不到致瘤细胞(MCF - 7乳腺癌细胞和HepG2肝癌细胞系)摄取量的20%。

结论

初步数据清楚地表明2 - NBDG可迅速摄取到肿瘤细胞中,可通过荧光成像分析进行监测。摄取表现出饱和性以及与D -葡萄糖的竞争性,这些都是2 - NBDG在癌细胞中摄取和保留所预期的特性。需要进行更多研究,包括其他恶性细胞系与对照细胞之间的比较,以全面表征2 - NBDG摄取的动力学特性以及这种2 - DG类似物作为恶性细胞葡萄糖摄取探针的潜在用途。

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