Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784716650834034688
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
work_keys_str_mv AT komenjob theeffectofdynamicinvivolikeoxaliplatinonhct116spheroidsinacanceronchipmodelisrepresentativeoftheresponseinxenografts
AT vanneervensannem theeffectofdynamicinvivolikeoxaliplatinonhct116spheroidsinacanceronchipmodelisrepresentativeoftheresponseinxenografts
AT bossinkelsbethgbm theeffectofdynamicinvivolikeoxaliplatinonhct116spheroidsinacanceronchipmodelisrepresentativeoftheresponseinxenografts
AT degrootninae theeffectofdynamicinvivolikeoxaliplatinonhct116spheroidsinacanceronchipmodelisrepresentativeoftheresponseinxenografts
AT nijmanlisannee theeffectofdynamicinvivolikeoxaliplatinonhct116spheroidsinacanceronchipmodelisrepresentativeoftheresponseinxenografts
AT vandenbergalbert theeffectofdynamicinvivolikeoxaliplatinonhct116spheroidsinacanceronchipmodelisrepresentativeoftheresponseinxenografts
AT vermeulenlouis theeffectofdynamicinvivolikeoxaliplatinonhct116spheroidsinacanceronchipmodelisrepresentativeoftheresponseinxenografts
AT vandermeerandriesd theeffectofdynamicinvivolikeoxaliplatinonhct116spheroidsinacanceronchipmodelisrepresentativeoftheresponseinxenografts
AT komenjob effectofdynamicinvivolikeoxaliplatinonhct116spheroidsinacanceronchipmodelisrepresentativeoftheresponseinxenografts
AT vanneervensannem effectofdynamicinvivolikeoxaliplatinonhct116spheroidsinacanceronchipmodelisrepresentativeoftheresponseinxenografts
AT bossinkelsbethgbm effectofdynamicinvivolikeoxaliplatinonhct116spheroidsinacanceronchipmodelisrepresentativeoftheresponseinxenografts
AT degrootninae effectofdynamicinvivolikeoxaliplatinonhct116spheroidsinacanceronchipmodelisrepresentativeoftheresponseinxenografts
AT nijmanlisannee effectofdynamicinvivolikeoxaliplatinonhct116spheroidsinacanceronchipmodelisrepresentativeoftheresponseinxenografts
AT vandenbergalbert effectofdynamicinvivolikeoxaliplatinonhct116spheroidsinacanceronchipmodelisrepresentativeoftheresponseinxenografts
AT vermeulenlouis effectofdynamicinvivolikeoxaliplatinonhct116spheroidsinacanceronchipmodelisrepresentativeoftheresponseinxenografts
AT vandermeerandriesd effectofdynamicinvivolikeoxaliplatinonhct116spheroidsinacanceronchipmodelisrepresentativeoftheresponseinxenografts