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Investigation of Drug Cocktail Effects on Cancer Cell-Spheroids Using a Microfluidic Drug-Screening Assay

Development of drugs based on potential anti-cancer chemotherapeutic agents has been hindered by its necessary tedious procedures and failure in the clinical trials because of unbearable toxicity and extremely low clinical efficacy. One of the technical challenges is the mismatch between laboratory...

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Autores principales: Au Ieong, Ka I., Yang, Chengpeng, Wong, Chin To, Shui, Angelie C., Wu, Tom T. Y., Chen, Ting-Hsuan, Lam, Raymond H. W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189953/
http://dx.doi.org/10.3390/mi8060167
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author Au Ieong, Ka I.
Yang, Chengpeng
Wong, Chin To
Shui, Angelie C.
Wu, Tom T. Y.
Chen, Ting-Hsuan
Lam, Raymond H. W.
author_facet Au Ieong, Ka I.
Yang, Chengpeng
Wong, Chin To
Shui, Angelie C.
Wu, Tom T. Y.
Chen, Ting-Hsuan
Lam, Raymond H. W.
author_sort Au Ieong, Ka I.
collection PubMed
description Development of drugs based on potential anti-cancer chemotherapeutic agents has been hindered by its necessary tedious procedures and failure in the clinical trials because of unbearable toxicity and extremely low clinical efficacy. One of the technical challenges is the mismatch between laboratory settings and human body environments for the cancer cells responding upon treatments of the anti-cancer agents. This major limitation urges for applying more reliable platforms for evaluating drugs with a higher throughput and cell aggregates in a more natural configuration. Here, we adopt a microfluidic device integrated with a differential micromixer and multiple microwell-containing channels (50 microwells per channel) for parallel screening of suspending cell spheroids treated by drugs with different combinations. We optimize the culture conditions of the surfactant-coated microwells in order to facilitate the spheroid formation of the breast cancer cell line (MDA-MB-231). We propose a new drug cocktail combined with three known chemotherapeutic agents (paclitaxel, epirubicin, and aspirin) for the drug screening of the cancer cell-spheroids. Our results exhibit the differential responses between planar cell layers in traditional culture wells and cell-spheroids grown in our microfluidic device, in terms of the apoptotic rates under treatments of the drug cocktails with different concentrations. These results reveal a distinct drug resistance between planar cell layers and cell-spheroids. Together, this work offers important guidelines on applying the cell-spheroid microfluidic cultures for development of more efficacious anticancer drugs.
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spelling pubmed-61899532018-11-01 Investigation of Drug Cocktail Effects on Cancer Cell-Spheroids Using a Microfluidic Drug-Screening Assay Au Ieong, Ka I. Yang, Chengpeng Wong, Chin To Shui, Angelie C. Wu, Tom T. Y. Chen, Ting-Hsuan Lam, Raymond H. W. Micromachines (Basel) Article Development of drugs based on potential anti-cancer chemotherapeutic agents has been hindered by its necessary tedious procedures and failure in the clinical trials because of unbearable toxicity and extremely low clinical efficacy. One of the technical challenges is the mismatch between laboratory settings and human body environments for the cancer cells responding upon treatments of the anti-cancer agents. This major limitation urges for applying more reliable platforms for evaluating drugs with a higher throughput and cell aggregates in a more natural configuration. Here, we adopt a microfluidic device integrated with a differential micromixer and multiple microwell-containing channels (50 microwells per channel) for parallel screening of suspending cell spheroids treated by drugs with different combinations. We optimize the culture conditions of the surfactant-coated microwells in order to facilitate the spheroid formation of the breast cancer cell line (MDA-MB-231). We propose a new drug cocktail combined with three known chemotherapeutic agents (paclitaxel, epirubicin, and aspirin) for the drug screening of the cancer cell-spheroids. Our results exhibit the differential responses between planar cell layers in traditional culture wells and cell-spheroids grown in our microfluidic device, in terms of the apoptotic rates under treatments of the drug cocktails with different concentrations. These results reveal a distinct drug resistance between planar cell layers and cell-spheroids. Together, this work offers important guidelines on applying the cell-spheroid microfluidic cultures for development of more efficacious anticancer drugs. MDPI 2017-05-24 /pmc/articles/PMC6189953/ http://dx.doi.org/10.3390/mi8060167 Text en © 2017 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Au Ieong, Ka I.
Yang, Chengpeng
Wong, Chin To
Shui, Angelie C.
Wu, Tom T. Y.
Chen, Ting-Hsuan
Lam, Raymond H. W.
Investigation of Drug Cocktail Effects on Cancer Cell-Spheroids Using a Microfluidic Drug-Screening Assay
title Investigation of Drug Cocktail Effects on Cancer Cell-Spheroids Using a Microfluidic Drug-Screening Assay
title_full Investigation of Drug Cocktail Effects on Cancer Cell-Spheroids Using a Microfluidic Drug-Screening Assay
title_fullStr Investigation of Drug Cocktail Effects on Cancer Cell-Spheroids Using a Microfluidic Drug-Screening Assay
title_full_unstemmed Investigation of Drug Cocktail Effects on Cancer Cell-Spheroids Using a Microfluidic Drug-Screening Assay
title_short Investigation of Drug Cocktail Effects on Cancer Cell-Spheroids Using a Microfluidic Drug-Screening Assay
title_sort investigation of drug cocktail effects on cancer cell-spheroids using a microfluidic drug-screening assay
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189953/
http://dx.doi.org/10.3390/mi8060167
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