Cokol-Cakmak Melike, Bakan Feray, Cetiner Selim, Cokol Murat
Faculty of Engineering and Natural Sciences, Sabanci University.
Nanotechnology Research and Application Center, Sabanci University.
J Vis Exp. 2018 Jun 21(136):57713. doi: 10.3791/57713.
A synergistic drug combination has a higher efficacy compared to the effects of individual drugs. Checkerboard assays, where drugs are combined in many doses, allow sensitive measurement of drug interactions. However, these assays are costly and do not scale well for measuring interaction among many drugs. Several recent studies have reported drug interaction measurements using a diagonal sampling of the traditional checkerboard assay. This alternative methodology greatly decreases the cost of drug interaction experiments and allows interaction measurement for combinations with many drugs. Here, we describe a protocol to measure the three pairwise interactions and one three-way interaction among three antibiotics in duplicate, in five days, using only three 96-well microplates and standard laboratory equipment. We present representative results showing that the three-antibiotic combination of Levofloxacin + Nalidixic Acid + Penicillin G is synergistic. Our protocol scales up to measure interactions among many drugs and in other biological contexts, allowing for efficient screens for multi-drug synergies against pathogens and tumors.
与单一药物的效果相比，协同药物组合具有更高的疗效。棋盘分析法将多种剂量的药物组合在一起，能够灵敏地测定药物相互作用。然而，这些分析成本高昂，对于测定多种药物之间的相互作用而言，扩展性不佳。最近的几项研究报告了使用传统棋盘分析法的对角线采样进行药物相互作用测定。这种替代方法大大降低了药物相互作用实验的成本，并允许对多种药物组合进行相互作用测定。在此，我们描述了一种方案，该方案只需使用三个96孔微孔板和标准实验室设备，就能在五天内对三种抗生素之间的三对两两相互作用和一种三药相互作用进行重复测量。我们展示了代表性结果，表明左氧氟沙星+萘啶酸+青霉素G的三联抗生素组合具有协同作用。我们的方案可扩展用于测定多种药物之间以及其他生物学背景下的相互作用，从而能够高效筛选针对病原体和肿瘤的多药协同作用。
