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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Online Access: | https://www.mdpi.com/2072-666X/13/5/739 |
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| author | Job Komen Sanne M. van Neerven Elsbeth G. B. M. Bossink Nina E. de Groot Lisanne E. Nijman Albert van den Berg Louis Vermeulen Andries D. van der Meer |
| author_facet | Job Komen Sanne M. van Neerven Elsbeth G. B. M. Bossink Nina E. de Groot Lisanne E. Nijman Albert van den Berg Louis Vermeulen Andries D. van der Meer |
| author_sort | Job Komen |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T03:23:44Z |
| format | Article |
| id | doaj.art-18db37a0126c41348682c3579ba25ad1 |
| institution | Directory Open Access Journal |
| issn | 2072-666X |
| language | English |
| last_indexed | 2024-03-10T03:23:44Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Micromachines |
| spelling | doaj.art-18db37a0126c41348682c3579ba25ad12023-11-23T12:12:25ZengMDPI AGMicromachines2072-666X2022-05-0113573910.3390/mi13050739The Effect of Dynamic, In Vivo-like Oxaliplatin on HCT116 Spheroids in a Cancer-on-Chip Model Is Representative of the Response in XenograftsJob Komen0Sanne M. van Neerven1Elsbeth G. B. M. Bossink2Nina E. de Groot3Lisanne E. Nijman4Albert van den Berg5Louis Vermeulen6Andries D. van der Meer7BIOS Lab on a Chip Group, MESA+ Institute for Nanotechnology, University of Twente, 7500 AE Enschede, The NetherlandsLaboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The NetherlandsLaboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The NetherlandsLaboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The NetherlandsLaboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The NetherlandsBIOS Lab on a Chip Group, MESA+ Institute for Nanotechnology, University of Twente, 7500 AE Enschede, The NetherlandsLaboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The NetherlandsApplied Stem Cell Technologies, TechMed Centre, University of Twente, 7500 AE Enschede, The NetherlandsThe 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.https://www.mdpi.com/2072-666X/13/5/739cancer-on-chipxenograftmicrofluidiccolorectal cancerpharmacodynamicspharmacokinetics |
| spellingShingle | Job Komen Sanne M. van Neerven Elsbeth G. B. M. Bossink Nina E. de Groot Lisanne E. Nijman Albert van den Berg Louis Vermeulen Andries D. van der Meer The Effect of Dynamic, In Vivo-like Oxaliplatin on HCT116 Spheroids in a Cancer-on-Chip Model Is Representative of the Response in Xenografts Micromachines cancer-on-chip xenograft microfluidic colorectal cancer pharmacodynamics pharmacokinetics |
| 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 | cancer-on-chip xenograft microfluidic colorectal cancer pharmacodynamics pharmacokinetics |
| url | https://www.mdpi.com/2072-666X/13/5/739 |
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