Traditionally, the monolayer (two-dimensional) cell cultures are used for initial evaluation of the effectiveness of anticancer drugs. In particular, these experiments provide the [Formula: see text] curves that determine drug concentration that can inhibit growth of a tumor colony by half when compared to the cells grown with no exposure to the drug. Low [Formula: see text] value means that the drug is effective at low concentrations, and thus will show lower systemic toxicity when administered to the patient. However, in these experiments cells are grown in a monolayer, all well exposed to the drug, while in vivo tumors expand as three-dimensional multicellular masses, where inner cells have a limited access to the drug. Therefore, we performed computational studies to compare the [Formula: see text] curves for cells grown as a two-dimensional monolayer and a cross section through a three-dimensional spheroid. Our results identified conditions (drug diffusivity, drug action mechanisms and cell proliferation capabilities) under which these [Formula: see text] curves differ significantly. This will help experimentalists to better determine drug dosage for future in vivo experiments and clinical trials.

中文翻译：

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单层和球状培养物中药物抑制作用 ($$\hbox {IC}_{50}$$) 的比较


传统上，单层（二维）细胞培养物用于初步评估抗癌药物的有效性。特别是，这些实验提供了[公式：见文本]曲线，该曲线确定了与未接触药物的情况下生长的细胞相比，可以将肿瘤集落的生长抑制一半的药物浓度。低[式：见文字]值意味着该药物在低浓度下有效，因此在给予患者时会表现出较低的全身毒性。然而，在这些实验中，细胞以单层形式生长，全部都充分暴露于药物，而体内肿瘤则以三维多细胞团的形式扩展，其中内部细胞接触药物的机会有限。因此，我们进行了计算研究，以比较二维单层细胞和三维球体横截面生长的细胞的[公式：参见文本]曲线。我们的结果确定了这些[公式：见文本]曲线显着差异的条件（药物扩散性、药物作用机制和细胞增殖能力）。这将有助于实验人员更好地确定未来体内实验和临床试验的药物剂量。