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Influence of a three-dimensional, microarray environment on human Cell culture in drug screening systems

Paper ID Volume ID Publish Year Pages File Format Full-Text
6604 502 2012 10 PDF Available
Title
Influence of a three-dimensional, microarray environment on human Cell culture in drug screening systems
Abstract

We have used a modified 3D cellular microarray platform for the high-throughput analysis of growth, cytotoxicity, and protein expression profile of a human hepatocellular carcinoma cell line, HepG2, in alginate. The results obtained were compared to analogous studies in 2D and 3D environments at the microtiter scale. The antiproliferative effects of four drugs, tamoxifen, 5-fluorouracil, doxorubicin, and amitriptyline, were studied as a function of seeding density in the three different culture platforms. The chemosensitivity of HepG2 cells to all four compounds decreased substantially with increasing cell number in the 2D and 3D microtiter-based cultures, while no seeding density dependence was observed in the IC50 values obtained in the 3D microarray culture platform. These results can be rationalized based on the development of confluence-dependent resistance in cultures where proliferation is restricted by cell–cell contacts and nutrient availability, as is the case for both of the microtiter-based cultures. Additionally, further development of an on-chip, in-cell immunofluorescence assay provided quantitative data on the levels of specific target proteins involved in proliferation, adhesion, angiogenesis and drug metabolism, and was used to compare expression profiles between 2D and 3D environments. The up-regulation of several CYP450 enzymes, β1-integrin and vascular endothelial growth factor (VEGF) in the 3D microarray cultures suggests that this platform provides a more in vivo-like environment allowing cells to approach their natural phenotype.

Keywords
3D cell culture; Microarray; High-throughput; Drug resistance
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Influence of a three-dimensional, microarray environment on human Cell culture in drug screening systems
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 35, December 2012, Pages 9087–9096
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us