Gabano Elisabetta, Colangelo Donato, Ghezzi Anna Rita, Osella Domenico
Dipartimento di Scienze dell'Ambiente e della Vita, Università del Piemonte Orientale A. Avogadro, Via Bellini 25/G, I-15100 Alessandria, Italy.
J Inorg Biochem. 2008 Apr;102(4):629-35. doi: 10.1016/j.jinorgbio.2007.10.006. Epub 2007 Oct 24.
Cellular uptake of a drug is one of the most important factors influencing its pharmacodynamics and pharmacokinetics. Our laboratory has previously studied platinum uptake following cisplatin, carboplatin and oxaliplatin treatment at sub-lethal doses of selected tumour cell lines. Here we report on the influence of temperature on dose-dependent antiproliferative effects, cellular uptake and DNA platination of these platinum-based drugs tested on MCF-7 human mammary carcinoma cell line. Inductively coupled plasma-mass spectrometry (ICP-MS) technique has been chosen to perform Pt determinations on cells treated with drug concentrations similar with those usually found in vivo in human plasma. The high sensitivity and analytical rapidity of this technique made possible to carry out a very large amount of Pt determinations (about 300) necessary for this study. Hyperthermia (43 degrees C) proved a synergistic effect with cisplatin on cell growth inhibition, while only an additive effect was demonstrated for carboplatin and oxaliplatin. This behaviour might be explained by the higher DNA platination ratio between data at 43 and 37 degrees C of cisplatin with respect to those of carboplatin and oxaliplatin.
药物的细胞摄取是影响其药效学和药代动力学的最重要因素之一。我们实验室之前研究了在选定肿瘤细胞系的亚致死剂量下，顺铂、卡铂和奥沙利铂处理后的铂摄取情况。在此，我们报告温度对在MCF-7人乳腺癌细胞系上测试的这些铂类药物的剂量依赖性抗增殖作用、细胞摄取和DNA铂化的影响。已选择电感耦合等离子体质谱（ICP-MS）技术对用与人体血浆中通常发现的浓度相似的药物浓度处理的细胞进行铂测定。该技术的高灵敏度和分析快速性使得能够进行本研究所需的大量铂测定（约300次）。热疗（43℃）证明与顺铂对细胞生长抑制有协同作用，而卡铂和奥沙利铂仅表现出相加作用。这种行为可能是由于顺铂在43℃和37℃时的数据之间的DNA铂化率高于卡铂和奥沙利铂。
