A Novel SimpleDrop Chip for 3D Spheroid Formation and Anti-Cancer Drug Assay

Cell culture is important for the rapid screening of anti-cancer drug candidates, attracting intense interest. Traditional 2D cell culture has been widely utilized in cancer biological research. However, 3D cellular spheroids are able to recapitulate the in vivo microenvironment of tissues or tumors...

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Main Authors: Xiaoli Liu, Huichao Lin, Jiaao Song, Taiyi Zhang, Xiaoying Wang, Xiaowen Huang, Chengyun Zheng
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Micromachines
Subjects:
Online Access:https://www.mdpi.com/2072-666X/12/6/681
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spelling doaj-b8916abae1e542969f2c8ff55904e0e12021-06-30T23:50:42ZengMDPI AGMicromachines2072-666X2021-06-011268168110.3390/mi12060681A Novel SimpleDrop Chip for 3D Spheroid Formation and Anti-Cancer Drug AssayXiaoli Liu0Huichao Lin1Jiaao Song2Taiyi Zhang3Xiaoying Wang4Xiaowen Huang5Chengyun Zheng6Department of Hematology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, ChinaState Key Laboratory of Biobased Material and Green Papermaking, Department of Bioengineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250300, ChinaState Key Laboratory of Biobased Material and Green Papermaking, Department of Bioengineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250300, ChinaState Key Laboratory of Biobased Material and Green Papermaking, Department of Bioengineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250300, ChinaDepartment of Pathology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, ChinaState Key Laboratory of Biobased Material and Green Papermaking, Department of Bioengineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250300, ChinaDepartment of Hematology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, ChinaCell culture is important for the rapid screening of anti-cancer drug candidates, attracting intense interest. Traditional 2D cell culture has been widely utilized in cancer biological research. However, 3D cellular spheroids are able to recapitulate the in vivo microenvironment of tissues or tumors. Thus far, several 3D cell culture methods have been developed, for instance, the hanging drop method, spinner flasks and micropatterned plates. Nevertheless, these methods have been reported to have some disadvantages, for example, medium replacement is inconvenient or causes cellular damage. Here, we report on an easy-to-operate and useful micro-hole culture chip (SimpleDrop) for 3D cellular spheroid formation and culture and drug analysis, which has advantages over the traditional method in terms of its ease of operation, lack of shear force and environmentally friendliness. On this chip, we observed the formation of a 3D spheroid clearly. Three drugs (paclitaxel, cisplatin and methotrexate) were tested by both cell viability assay and drug-induced apoptotic assay. The results show that the three drugs present a similar conclusion: cell viability decreased over time and concentration. Moreover, the apoptotic experiment showed a similar trend to the live/dead cell assay, in that the fraction of the apoptotic and necrotic cells correlated with the concentration and time. All these results prove that our SimpleDrop method is a useful and easy method for the formation of 3D cellular spheroids, which shows its potential for both cell–cell interaction research, tissue engineering and anticancer drug screening.https://www.mdpi.com/2072-666X/12/6/681cell culture3D cell spherescancerdrug assaymicro-hole culture chip
collection DOAJ
language English
format Article
sources DOAJ
author Xiaoli Liu
Huichao Lin
Jiaao Song
Taiyi Zhang
Xiaoying Wang
Xiaowen Huang
Chengyun Zheng
spellingShingle Xiaoli Liu
Huichao Lin
Jiaao Song
Taiyi Zhang
Xiaoying Wang
Xiaowen Huang
Chengyun Zheng
A Novel SimpleDrop Chip for 3D Spheroid Formation and Anti-Cancer Drug Assay
Micromachines
cell culture
3D cell spheres
cancer
drug assay
micro-hole culture chip
author_facet Xiaoli Liu
Huichao Lin
Jiaao Song
Taiyi Zhang
Xiaoying Wang
Xiaowen Huang
Chengyun Zheng
author_sort Xiaoli Liu
title A Novel SimpleDrop Chip for 3D Spheroid Formation and Anti-Cancer Drug Assay
title_short A Novel SimpleDrop Chip for 3D Spheroid Formation and Anti-Cancer Drug Assay
title_full A Novel SimpleDrop Chip for 3D Spheroid Formation and Anti-Cancer Drug Assay
title_fullStr A Novel SimpleDrop Chip for 3D Spheroid Formation and Anti-Cancer Drug Assay
title_full_unstemmed A Novel SimpleDrop Chip for 3D Spheroid Formation and Anti-Cancer Drug Assay
title_sort novel simpledrop chip for 3d spheroid formation and anti-cancer drug assay
publisher MDPI AG
series Micromachines
issn 2072-666X
publishDate 2021-06-01
description Cell culture is important for the rapid screening of anti-cancer drug candidates, attracting intense interest. Traditional 2D cell culture has been widely utilized in cancer biological research. However, 3D cellular spheroids are able to recapitulate the in vivo microenvironment of tissues or tumors. Thus far, several 3D cell culture methods have been developed, for instance, the hanging drop method, spinner flasks and micropatterned plates. Nevertheless, these methods have been reported to have some disadvantages, for example, medium replacement is inconvenient or causes cellular damage. Here, we report on an easy-to-operate and useful micro-hole culture chip (SimpleDrop) for 3D cellular spheroid formation and culture and drug analysis, which has advantages over the traditional method in terms of its ease of operation, lack of shear force and environmentally friendliness. On this chip, we observed the formation of a 3D spheroid clearly. Three drugs (paclitaxel, cisplatin and methotrexate) were tested by both cell viability assay and drug-induced apoptotic assay. The results show that the three drugs present a similar conclusion: cell viability decreased over time and concentration. Moreover, the apoptotic experiment showed a similar trend to the live/dead cell assay, in that the fraction of the apoptotic and necrotic cells correlated with the concentration and time. All these results prove that our SimpleDrop method is a useful and easy method for the formation of 3D cellular spheroids, which shows its potential for both cell–cell interaction research, tissue engineering and anticancer drug screening.
topic cell culture
3D cell spheres
cancer
drug assay
micro-hole culture chip
url https://www.mdpi.com/2072-666X/12/6/681
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