缺氧诱导MCF7细胞中氟代脱氧葡萄糖摄取增加。

Hypoxia-Induced increase in FDG uptake in MCF7 cells.

作者信息

Burgman P, Odonoghue J A, Humm J L, Ling C C

机构信息

Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

出版信息

J Nucl Med. 2001 Jan;42(1):170-5.

PMID:11197971

Abstract

UNLABELLED

Recent clinical data indicate that tumor hypoxia negatively affects the treatment outcome of both radiotherapy and surgery in various cancers, emphasizing the need for noninvasive detection of tumor hypoxia. Several studies have shown an increased uptake of FDG in hypoxic regions of xenografts, suggesting the use of PET with FDG as a potential technique. In this study, we examine the mechanism underlying the hypoxia-induced increase of FDG uptake in the human breast carcinoma cell line MCF7.

METHODS

The uptake of 3H-FDG into MCF7 cells was determined after incubation under hypoxic (0% oxygen) or normoxic conditions, with or without redox agents, for varying time periods. In addition, the effects of the redox agents on the glucose transporter activity and the hexokinase activity were determined independently, and the effects of hypoxia on glucose transporter protein and hexokinase levels were assessed.

RESULTS

A more than twofold increase (2.53 +/- 0.79; P < 0.005) in 3H-FDG uptake was observed under hypoxic conditions, but no changes in the cellular levels of glucose transporter proteins or hexokinase were observed. A reducing agent, dithiothreitol (DTT), also caused an increase in 3H-FDG uptake but failed to affect uptake under hypoxic conditions. This indicates that the mechanisms by which hypoxia and DTT affect 3H-FDG uptake might be the same. The oxidizing agent p-chloromercuribenzenesulfonic acid (pCMBS) had no effect on 3H-FDG uptake under normoxic conditions but counteracted the effect of hypoxia. DTT caused an increase in glucose transporter activity, whereas it had no effect on hexokinase activity. pCMBS had no effect on either glucose transporter activity or hexokinase activity.

CONCLUSION

The hypoxia-induced increase in 3H-FDG uptake in MCF7 cells is the result, in part, of an increase in glucose transporter activity resulting from the modification (reduction) of thiol group(s) in the glucose transport protein(s). Modulation of hexokinase activity is probably not involved in the hypoxia-induced increase in 3H-FDG uptake in these cells.

摘要

未标注

近期临床数据表明，肿瘤缺氧对多种癌症的放疗和手术治疗效果均产生负面影响，这凸显了对肿瘤缺氧进行无创检测的必要性。多项研究显示，异种移植瘤缺氧区域的氟代脱氧葡萄糖（FDG）摄取增加，提示使用FDG正电子发射断层扫描（PET）作为一种潜在技术。在本研究中，我们探究了人乳腺癌细胞系MCF7中缺氧诱导FDG摄取增加的机制。

方法

在缺氧（0%氧气）或常氧条件下，加入或不加入氧化还原试剂，孵育不同时间段后，测定3H-FDG进入MCF7细胞的摄取情况。此外，分别测定氧化还原试剂对葡萄糖转运蛋白活性和己糖激酶活性的影响，并评估缺氧对葡萄糖转运蛋白和己糖激酶水平的影响。

结果

在缺氧条件下，观察到3H-FDG摄取增加了两倍多（2.53±0.79；P<0.005），但葡萄糖转运蛋白或己糖激酶的细胞水平未观察到变化。还原剂二硫苏糖醇（DTT）也导致3H-FDG摄取增加，但在缺氧条件下未能影响摄取。这表明缺氧和DTT影响3H-FDG摄取的机制可能相同。氧化剂对氯汞苯磺酸（pCMBS）在常氧条件下对3H-FDG摄取无影响，但可抵消缺氧的作用。DTT导致葡萄糖转运蛋白活性增加，而对己糖激酶活性无影响。pCMBS对葡萄糖转运蛋白活性或己糖激酶活性均无影响。