Cargando…

A Cancer Spheroid Array Chip for Selecting Effective Drug

A cancer spheroid array chip was developed by modifying a micropillar and microwell structure to improve the evaluation of drugs targeting specific mutations such as phosphor-epidermal growth factor receptor (p-EGFR). The chip encapsulated cells in alginate and allowed cancer cells to grow for over...

Descripción completa

Detalles Bibliográficos
Autores principales: Choi, Jae Won, Lee, Sang-Yun, Lee, Dong Woo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843395/
https://www.ncbi.nlm.nih.gov/pubmed/31614722
http://dx.doi.org/10.3390/mi10100688
_version_ 1783468205287669760
author Choi, Jae Won
Lee, Sang-Yun
Lee, Dong Woo
author_facet Choi, Jae Won
Lee, Sang-Yun
Lee, Dong Woo
author_sort Choi, Jae Won
collection PubMed
description A cancer spheroid array chip was developed by modifying a micropillar and microwell structure to improve the evaluation of drugs targeting specific mutations such as phosphor-epidermal growth factor receptor (p-EGFR). The chip encapsulated cells in alginate and allowed cancer cells to grow for over seven days to form cancer spheroids. However, reagents or media used to screen drugs in a high-density spheroid array had to be replaced very carefully, and this was a tedious task. Particularly, the immunostaining of cancer spheroids required numerous steps to replace many of the reagents used for drug evaluation. To solve this problem, we adapted a micropillar and microwell structure to a spheroid array. Thus, culturing cancer spheroids in alginate spots attached to the micropillar allowed us to replace the reagents in the microwell chip with a single fill of fresh medium, without damaging the cancer spheroids. In this study, a cancer spheroid array was made from a p-EGFR-overexpressing cell line (A549 lung cancer cell line). In a 12 by 36 column array chip (25 mm by 75 mm), the spheroid over 100 µm in diameter started to form at day seven and p-EGFR was also considerably overexpressed. The array was used for p-EGFR inhibition and cell viability measurement against seventy drugs, including ten EGFR-targeting drugs. By comparing drug response in the spheroid array (spheroid model) with that in the single-cell model, we demonstrated that the two models showed different responses and that the spheroid model might be more resistant to some drugs, thus narrowing the choice of drug candidates.
format Online
Article
Text
id pubmed-6843395
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-68433952019-11-25 A Cancer Spheroid Array Chip for Selecting Effective Drug Choi, Jae Won Lee, Sang-Yun Lee, Dong Woo Micromachines (Basel) Article A cancer spheroid array chip was developed by modifying a micropillar and microwell structure to improve the evaluation of drugs targeting specific mutations such as phosphor-epidermal growth factor receptor (p-EGFR). The chip encapsulated cells in alginate and allowed cancer cells to grow for over seven days to form cancer spheroids. However, reagents or media used to screen drugs in a high-density spheroid array had to be replaced very carefully, and this was a tedious task. Particularly, the immunostaining of cancer spheroids required numerous steps to replace many of the reagents used for drug evaluation. To solve this problem, we adapted a micropillar and microwell structure to a spheroid array. Thus, culturing cancer spheroids in alginate spots attached to the micropillar allowed us to replace the reagents in the microwell chip with a single fill of fresh medium, without damaging the cancer spheroids. In this study, a cancer spheroid array was made from a p-EGFR-overexpressing cell line (A549 lung cancer cell line). In a 12 by 36 column array chip (25 mm by 75 mm), the spheroid over 100 µm in diameter started to form at day seven and p-EGFR was also considerably overexpressed. The array was used for p-EGFR inhibition and cell viability measurement against seventy drugs, including ten EGFR-targeting drugs. By comparing drug response in the spheroid array (spheroid model) with that in the single-cell model, we demonstrated that the two models showed different responses and that the spheroid model might be more resistant to some drugs, thus narrowing the choice of drug candidates. MDPI 2019-10-12 /pmc/articles/PMC6843395/ /pubmed/31614722 http://dx.doi.org/10.3390/mi10100688 Text en © 2019 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
Choi, Jae Won
Lee, Sang-Yun
Lee, Dong Woo
A Cancer Spheroid Array Chip for Selecting Effective Drug
title A Cancer Spheroid Array Chip for Selecting Effective Drug
title_full A Cancer Spheroid Array Chip for Selecting Effective Drug
title_fullStr A Cancer Spheroid Array Chip for Selecting Effective Drug
title_full_unstemmed A Cancer Spheroid Array Chip for Selecting Effective Drug
title_short A Cancer Spheroid Array Chip for Selecting Effective Drug
title_sort cancer spheroid array chip for selecting effective drug
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843395/
https://www.ncbi.nlm.nih.gov/pubmed/31614722
http://dx.doi.org/10.3390/mi10100688
work_keys_str_mv AT choijaewon acancerspheroidarraychipforselectingeffectivedrug
AT leesangyun acancerspheroidarraychipforselectingeffectivedrug
AT leedongwoo acancerspheroidarraychipforselectingeffectivedrug
AT choijaewon cancerspheroidarraychipforselectingeffectivedrug
AT leesangyun cancerspheroidarraychipforselectingeffectivedrug
AT leedongwoo cancerspheroidarraychipforselectingeffectivedrug