定量化检测:癌症信号通路的抑制。
Quantifying assays: Inhibition of signalling pathways of cancer.
发表日期:2023 Sep 05
作者:
Roumen Anguelov, G Manjunath, Avulundiah E Phiri, Trevor T Nyakudya, Priyesh Bipath, June C Serem, Yvette N Hlophe
来源:
Cell Death & Disease
摘要:
抑制信号传导途径涉及对癌细胞的生存能力、细胞分裂和死亡过程进行控制。为了检测被测试的药物的分子结构是否具有所需的抑制特性,经常会创建一种测定方案,但在不同实验中,这些方案往往会出现很大的可变性。在进行推断时,必须减小这种可变性的影响是至关重要的。在本文中,我们提出通过数学模型描绘抑制机制和激活-抑制动力学的视角来研究实验数据。该方法以对黑色素瘤细胞的趋化因子受体4(CXCR4)和趋化因子配体12(CXCL12)信号通路抑制的实验研究获得的测定数据为例进行说明。定量分析是一个分为两个步骤的过程:(i)从模型中理论上推导出细胞生存能力作为时间的函数,取决于几个参数;(ii)通过使用实验数据估计参数的值。细胞生存能力是作为抑制剂的浓度和时间的函数获得的,从而全面描述了考虑的抑制剂的潜在治疗效果,例如可以计算任意时间点的IC50(半数抑制浓度)。© 作者们2023年。由牛津大学出版社代表数学研究所出版。保留所有权利。
Inhibiting a signalling pathway concerns controlling the cellular processes of a cancer cell's viability, cell division, and death. Assay protocols created to see if the molecular structures of the drugs being tested have the desired inhibition qualities often show great variability across experiments, and it is imperative to diminish the effects of such variability while inferences are drawn. In this paper we propose the study of experimental data through the lenses of a mathematical model depicting the inhibition mechanism and the activation-inhibition dynamics. The method is exemplified through assay data obtained from an experimental study of the inhibition of the chemokine receptor 4 (CXCR4) and chemokine ligand 12 (CXCL12) signalling pathway of melanoma cells. The quantitative analysis is conducted as a two step process: (i) Deriving theoretically from the model the cell viability as a function of time depending on several parameters; (ii) Estimating the values of the parameters by using the experimental data. The cell viability is obtained as a function of concentration of the inhibitor and time, thus providing a comprehensive characterization of the potential therapeutic effect of the considered inhibitor, e.g. IC50 can be computed for any time point.© The Author(s) 2023. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.