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Title: Emergence of spatio-temporal variations in chemotherapeutic drug efficacy : in-vitro and in-silico 3D tumour spheroid studies
Authors: Sheraton, Muniraj Vivek
Chiew, Geraldine Giap Ying
Melnikov, Valentin
Tan, E. Y.
Luo, K. Q.
Verma, N.
Sloot, Peter M. A.
Keywords: Science::Medicine
Issue Date: 2020
Source: Sheraton, M. V., Chiew, G. G. Y., Melnikov, V., Tan, E. Y., Luo, K. Q., Verma, N., & Sloot, P. M. A. (2020). Emergence of spatio-temporal variations in chemotherapeutic drug efficacy : in-vitro and in-silico 3D tumour spheroid studies. BMC Cancer, 20(1), 1201-. doi:10.1186/s12885-020-07677-5
Journal: BMC Cancer
Abstract: Background: The mechanisms of action and efficacy of cisplatin and paclitaxel at cell population level are well studied and documented, however the localized spatio-temporal effects of the drugs are less well understood. We explore the emergence of spatially preferential drug efficacy resulting from variations in mechanisms of cell-drug interactions. Methods: 3D spheroids of HeLa-C3 cells were treated with drugs, cisplatin and paclitaxel. This was followed by sectioning and staining of the spheroids to track the spatio-temporal apoptotic effects of the drugs. A mechanistic drug-cell interaction model was developed and simulated to analyse the localized efficacy of these drugs. Results: The outcomes of drug actions on a local cell population was dependant on the interactions between cell repair probability, intracellular drug concentration and cell’s mitosis phase. In spheroids treated with cisplatin, drug induced apoptosis is found to be scattered throughout the volume of the spheroids. In contrast, effect of paclitaxel is found to be preferentially localized along the periphery of the spheroids. Combinatorial treatments of cisplatin and paclitaxel result in varying levels of cell apoptosis based on the scheduling strategy. Conclusions: The preferential action of paclitaxel can be attributed to the cell characteristics of the peripheral population. The model simulations and experimental data show that treatments initiated with paclitaxel are more efficacious due to the cascading of spatial effects of the drugs.
ISSN: 1471-2407
DOI: 10.1186/s12885-020-07677-5
Rights: © 2020 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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