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The Effect of Dynamic, In Vivo-like Oxaliplatin on HCT116 Spheroids in a Cancer-on-Chip Model Is Representative of the Response in Xenografts
The cancer xenograft model in which human cancer cells are implanted in a mouse is one of the most used preclinical models to test the efficacy of novel cancer drugs. However, the model is imperfect; animal models are ethically burdened, and the imperfect efficacy predictions contribute to high clin...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146796/ https://www.ncbi.nlm.nih.gov/pubmed/35630206 http://dx.doi.org/10.3390/mi13050739 |
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author | Komen, Job van Neerven, Sanne M. Bossink, Elsbeth G. B. M. de Groot, Nina E. Nijman, Lisanne E. van den Berg, Albert Vermeulen, Louis van der Meer, Andries D. |
author_facet | Komen, Job van Neerven, Sanne M. Bossink, Elsbeth G. B. M. de Groot, Nina E. Nijman, Lisanne E. van den Berg, Albert Vermeulen, Louis van der Meer, Andries D. |
author_sort | Komen, Job |
collection | PubMed |
description | The cancer xenograft model in which human cancer cells are implanted in a mouse is one of the most used preclinical models to test the efficacy of novel cancer drugs. However, the model is imperfect; animal models are ethically burdened, and the imperfect efficacy predictions contribute to high clinical attrition of novel drugs. If microfluidic cancer-on-chip models could recapitulate key elements of the xenograft model, then these models could substitute the xenograft model and subsequently surpass the xenograft model by reducing variation, increasing sensitivity and scale, and adding human factors. Here, we exposed HCT116 colorectal cancer spheroids to dynamic, in vivo-like, concentrations of oxaliplatin, including a 5 day drug-free period, on-chip. Growth inhibition on-chip was comparable to existing xenograft studies. Furthermore, immunohistochemistry showed a similar response in proliferation and apoptosis markers. While small volume changes in xenografts are hard to detect, in the chip-system, we could observe a temporary growth delay. Lastly, histopathology and a pharmacodynamic model showed that the cancer spheroid-on-chip was representative of the proliferating outer part of a HCT116 xenograft, thereby capturing the major driver of the drug response of the xenograft. Hence, the cancer-on-chip model recapitulated the response of HCT116 xenografts to oxaliplatin and provided additional drug efficacy information. |
format | Online Article Text |
id | pubmed-9146796 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91467962022-05-29 The Effect of Dynamic, In Vivo-like Oxaliplatin on HCT116 Spheroids in a Cancer-on-Chip Model Is Representative of the Response in Xenografts Komen, Job van Neerven, Sanne M. Bossink, Elsbeth G. B. M. de Groot, Nina E. Nijman, Lisanne E. van den Berg, Albert Vermeulen, Louis van der Meer, Andries D. Micromachines (Basel) Article The cancer xenograft model in which human cancer cells are implanted in a mouse is one of the most used preclinical models to test the efficacy of novel cancer drugs. However, the model is imperfect; animal models are ethically burdened, and the imperfect efficacy predictions contribute to high clinical attrition of novel drugs. If microfluidic cancer-on-chip models could recapitulate key elements of the xenograft model, then these models could substitute the xenograft model and subsequently surpass the xenograft model by reducing variation, increasing sensitivity and scale, and adding human factors. Here, we exposed HCT116 colorectal cancer spheroids to dynamic, in vivo-like, concentrations of oxaliplatin, including a 5 day drug-free period, on-chip. Growth inhibition on-chip was comparable to existing xenograft studies. Furthermore, immunohistochemistry showed a similar response in proliferation and apoptosis markers. While small volume changes in xenografts are hard to detect, in the chip-system, we could observe a temporary growth delay. Lastly, histopathology and a pharmacodynamic model showed that the cancer spheroid-on-chip was representative of the proliferating outer part of a HCT116 xenograft, thereby capturing the major driver of the drug response of the xenograft. Hence, the cancer-on-chip model recapitulated the response of HCT116 xenografts to oxaliplatin and provided additional drug efficacy information. MDPI 2022-05-06 /pmc/articles/PMC9146796/ /pubmed/35630206 http://dx.doi.org/10.3390/mi13050739 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Komen, Job van Neerven, Sanne M. Bossink, Elsbeth G. B. M. de Groot, Nina E. Nijman, Lisanne E. van den Berg, Albert Vermeulen, Louis van der Meer, Andries D. The Effect of Dynamic, In Vivo-like Oxaliplatin on HCT116 Spheroids in a Cancer-on-Chip Model Is Representative of the Response in Xenografts |
title | The Effect of Dynamic, In Vivo-like Oxaliplatin on HCT116 Spheroids in a Cancer-on-Chip Model Is Representative of the Response in Xenografts |
title_full | The Effect of Dynamic, In Vivo-like Oxaliplatin on HCT116 Spheroids in a Cancer-on-Chip Model Is Representative of the Response in Xenografts |
title_fullStr | The Effect of Dynamic, In Vivo-like Oxaliplatin on HCT116 Spheroids in a Cancer-on-Chip Model Is Representative of the Response in Xenografts |
title_full_unstemmed | The Effect of Dynamic, In Vivo-like Oxaliplatin on HCT116 Spheroids in a Cancer-on-Chip Model Is Representative of the Response in Xenografts |
title_short | The Effect of Dynamic, In Vivo-like Oxaliplatin on HCT116 Spheroids in a Cancer-on-Chip Model Is Representative of the Response in Xenografts |
title_sort | effect of dynamic, in vivo-like oxaliplatin on hct116 spheroids in a cancer-on-chip model is representative of the response in xenografts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146796/ https://www.ncbi.nlm.nih.gov/pubmed/35630206 http://dx.doi.org/10.3390/mi13050739 |
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