O'Neil Roger G, Wu Ling, Mullani Nizar
Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, 6431 Fannin, Houston, TX 77030, USA.
Mol Imaging Biol. 2005 Nov-Dec;7(6):388-92. doi: 10.1007/s11307-005-0011-6.
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.
MCF-7 breast cancer epithelial cells were grown and plated on coverslips for analysis of 2-NBDG uptake via fluorescence imaging microscopy.
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.
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.
[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。
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。
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%。
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。