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首页> 美国卫生研究院文献>International Journal of Molecular Imaging >18FFluoro-2-Deoxy-D-Glucose Incorporation by MCF-7 Breast TumourCells In Vitro Is Modulated by Treatment with TamoxifenDoxorubicin and Docetaxel: Relationship to Chemotherapy-InducedChanges in ATP Content Hexokinase Activity and Glucose Transport
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18FFluoro-2-Deoxy-D-Glucose Incorporation by MCF-7 Breast TumourCells In Vitro Is Modulated by Treatment with TamoxifenDoxorubicin and Docetaxel: Relationship to Chemotherapy-InducedChanges in ATP Content Hexokinase Activity and Glucose Transport

机译：18F MCF-7乳腺肿瘤掺入氟-2-脱氧-D-葡萄糖他莫昔芬治疗可调节体外细胞阿霉素和多西他赛：与化学疗法诱导的关系ATP含量己糖激酶活性和葡萄糖转运的变化

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Breast tumours responding to chemotherapy exhibit decreased [18F]fluoro-2-deoxy-D-glucose ([18F]FDG) incorporation. Underlying mechanisms of these changes is poorly understood. Here, in MCF-7 cells, responding to chemotherapy drugs commonly utilised in the treatment of breast cancer, [18F]FDG incorporation and several pivotal factors associated with [18F]FDG incorporation investigated. Methods. IC50 and subclinical doxorubicin, docetaxel, and tamoxifen doses determined using MTT assay. [18F]FDG incorporation by cells treated with IC50 drug doses for 48 hours and 72 hours were determined and FDG dephosphorylation estimated by measuring loss of 18F from [18F]FDG-preincubated cells (pulse-chase). Glucose transport determined by measuring initial uptake rate of non-metabolised glucose analogue omethylglucose; hexokinase activity and ATP content measured in cell homogenates; Cell cycle distribution determined using flow cytometry of propidium iodide stained nuclei. Results. [18F]FDG incorporation and ATP content decreased in cells after 72 hours treatment with IC50 doses of tamoxifen, doxorubicin, and docetaxel compared with untreated controls. Decreased glucose transport and/or hexokinase activity accompanied decreased [18F]FDG incorporation by MCF-7 cells treated with tamoxifen or doxorubicin but not docetaxel. Conclusions. Tumour cell [18F]FDG incorporation along with ATP content decreased by treatment with tamoxifen, doxorubicin and docetaxel paralleling clinical observations for solid tumours. Effect of each treatment on glucose transport and hexokinase activity was chemotherapy-drug dependent.
机译：对化疗有反应的乳腺肿瘤的[ 18 F]氟-2-脱氧-D-葡萄糖（[ 18 F] FDG）掺入减少。这些变化的潜在机制知之甚少。在这里，在MCF-7细胞中，对通常用于治疗乳腺癌的化疗药物，[ 18 F] FDG的掺入以及与[ 18 F相关的几个关键因素有反应] FDG公司成立进行了调查。方法。使用MTT分析法确定IC50和亚临床阿霉素，多西他赛和他莫昔芬的剂量。确定通过IC50药物处理48小时和72小时的细胞中[ 18 F] FDG的掺入，并通过测量[ 18 F] FDG中18F的损失来估算FDG的去磷酸化作用-预孵育的细胞（脉冲追踪）。通过测量未代谢的葡萄糖类似物邻甲基葡萄糖的初始摄取率来确定葡萄糖转运；在细胞匀浆中测出的己糖激酶活性和ATP含量;使用碘化丙啶染色的核的流式细胞术确定细胞周期分布。结果。与未处理的对照组相比，IC50剂量的他莫昔芬，阿霉素和多西他赛处理72小时后，细胞中[ 18 F] FDG的掺入和ATP含量降低。用他莫昔芬或阿霉素而非多西紫杉醇处理的MCF-7细胞降低的葡萄糖转运和/或己糖激酶活性伴随着[ 18 F] FDG掺入的减少。结论。他莫昔芬，阿霉素和多西他赛治疗可降低肿瘤细胞[ 18 F] FDG的掺入以及ATP含量，与实体瘤的临床观察结果相似。每种治疗对葡萄糖转运和己糖激酶活性的影响是化疗药物依赖性的。

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