关键词： ADP, adenosine diphosphate AMP, adenosine monophosphate ANOVA, analysis of variance ATP, adenosine triphosphate AUC, area under the curve Antibiotic anticancer drugs CDP, cytidine diphosphate CTP, cytidine triphosphate DMEM, Dulbecco׳s modified eagle׳s cell culture media DMSO, dimethyl sulfoxide DNA, deoxyribonucleic acid EC, energy charge EDTA, ethylene diamine tetra-acetic acid FCS, fetal calf serum GDP, guanosine diphosphate GMP, guanosine monophosphate GTP, guanosine triphosphate HEPES, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid Ion-pair HPLC MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Mechanisms of antitumor drug action Nucleotides PBS, phosphate buffered saline PCA, principal component analysis Potential biomarkers Principal component analysis RNA, ribonucleic acid ROC, receiver operating characteristic RPMI-1640, Roswell Park Memorial Institute-1640 TBAHS, tetrabutylammonium hydrogen sulfate TCA, trichloroacetic acid Targeted metabolomics analysis Tumor cells UDP, uridine diphosphate UTP, uridine triphosphate dATP, deoxyadenosine triphosphate dCDP, deoxycytidine diphosphate dCTP, deoxycytidine triphosphate dGMP, deoxyribonucleic monophosphate dGTP, deoxyguanosine triphosphate dUDP, deoxyuridine diphpsphate dUTP, deoxyuridine triphosphate

来  源：   DOI：10.1016/j.apsb.2015.03.010

Abstract：
Nucleotide pools in mammalian cells change due to the influence of antitumor drugs, which may help in evaluating the drug effect and understanding the mechanism of drug action. In this study, an ion-pair RP-HPLC method was used for a simple, sensitive and simultaneous determination of the levels of 12 nucleotides in mammalian cells treated with antibiotic antitumor drugs (daunorubicin, epirubicin and dactinomycin D). Through the use of this targeted metabolomics approach to find potential biomarkers, UTP and ATP were verified to be the most appropriate biomarkers. Moreover, a holistic statistical approach was put forward to develop a model which could distinguish 4 categories of drugs with different mechanisms of action. This model can be further validated by evaluating drugs with different mechanisms of action. This targeted metabolomics study may provide a novel approach to predict the mechanism of action of antitumor drugs.
摘要：
由于抗肿瘤药物的影响，哺乳动物细胞中的核苷酸库发生变化，这可能有助于评估药物作用和理解药物作用机制。在这项研究中,离子对RP-HPLC方法用于一种简单的，敏感且同时测定用抗生素抗肿瘤药物处理的哺乳动物细胞中12个核苷酸的水平（柔红霉素，表柔比星和放线菌素D）。通过使用这种靶向代谢组学方法来寻找潜在的生物标志物，UTP和ATP被证实是最合适的生物标志物。此外，提出了一种整体统计方法，以建立一个模型，可以区分4种具有不同作用机制的药物。可以通过评估具有不同作用机制的药物来进一步验证该模型。这种靶向代谢组学研究可能为预测抗肿瘤药物的作用机制提供了一种新的方法。
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