Cargando…
Evaluating Inhibition of the Epidermal Growth Factor (EGF)-Induced Response of Mutant MCF10A Cells with an Acoustic Sensor
Many cancer treatments rely on inhibition of epidermal growth factor (EGF)-induced cellular responses. Evaluating drug effects on such responses becomes critical to the development of new cancer therapeutics. In this report, we have employed a label-free acoustic sensor, the quartz crystal microbala...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263556/ https://www.ncbi.nlm.nih.gov/pubmed/25586035 http://dx.doi.org/10.3390/bios2040448 |
_version_ | 1782348596129038336 |
---|---|
author | Garcia, Marcela P. Shahid, Ammar Chen, Jennifer Y. Xi, Jun |
author_facet | Garcia, Marcela P. Shahid, Ammar Chen, Jennifer Y. Xi, Jun |
author_sort | Garcia, Marcela P. |
collection | PubMed |
description | Many cancer treatments rely on inhibition of epidermal growth factor (EGF)-induced cellular responses. Evaluating drug effects on such responses becomes critical to the development of new cancer therapeutics. In this report, we have employed a label-free acoustic sensor, the quartz crystal microbalance with dissipation monitoring (QCM-D), to track the EGF-induced response of mutant MCF10A cells under various inhibitory conditions. We have identified a complex cell de-adhesion process, which can be distinctly altered by inhibitors of signaling pathways and cytoskeleton formation in a dose-dependent manner. The dose dependencies of the inhibitors provide IC(50) values which are in strong agreement with the values reported in the literature, demonstrating the sensitivity and reliability of the QCM-D as a screening tool. Using immunofluorescence imaging, we have also verified the quantitative relationship between the ΔD-response (change in energy dissipation factor) and the level of focal adhesions quantified with the areal density of immunostained vinculin under those inhibitory conditions. Such a correlation suggests that the dynamic restructuring of focal adhesions can be assessed based on the time-dependent change in ΔD-response. Overall, this report has shown that the QCM-D has the potential to become an effective sensing platform for screening therapeutic agents that target signaling and cytoskeletal proteins. |
format | Online Article Text |
id | pubmed-4263556 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-42635562015-01-13 Evaluating Inhibition of the Epidermal Growth Factor (EGF)-Induced Response of Mutant MCF10A Cells with an Acoustic Sensor Garcia, Marcela P. Shahid, Ammar Chen, Jennifer Y. Xi, Jun Biosensors (Basel) Article Many cancer treatments rely on inhibition of epidermal growth factor (EGF)-induced cellular responses. Evaluating drug effects on such responses becomes critical to the development of new cancer therapeutics. In this report, we have employed a label-free acoustic sensor, the quartz crystal microbalance with dissipation monitoring (QCM-D), to track the EGF-induced response of mutant MCF10A cells under various inhibitory conditions. We have identified a complex cell de-adhesion process, which can be distinctly altered by inhibitors of signaling pathways and cytoskeleton formation in a dose-dependent manner. The dose dependencies of the inhibitors provide IC(50) values which are in strong agreement with the values reported in the literature, demonstrating the sensitivity and reliability of the QCM-D as a screening tool. Using immunofluorescence imaging, we have also verified the quantitative relationship between the ΔD-response (change in energy dissipation factor) and the level of focal adhesions quantified with the areal density of immunostained vinculin under those inhibitory conditions. Such a correlation suggests that the dynamic restructuring of focal adhesions can be assessed based on the time-dependent change in ΔD-response. Overall, this report has shown that the QCM-D has the potential to become an effective sensing platform for screening therapeutic agents that target signaling and cytoskeletal proteins. MDPI 2012-11-13 /pmc/articles/PMC4263556/ /pubmed/25586035 http://dx.doi.org/10.3390/bios2040448 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Garcia, Marcela P. Shahid, Ammar Chen, Jennifer Y. Xi, Jun Evaluating Inhibition of the Epidermal Growth Factor (EGF)-Induced Response of Mutant MCF10A Cells with an Acoustic Sensor |
title | Evaluating Inhibition of the Epidermal Growth Factor (EGF)-Induced Response of Mutant MCF10A Cells with an Acoustic Sensor |
title_full | Evaluating Inhibition of the Epidermal Growth Factor (EGF)-Induced Response of Mutant MCF10A Cells with an Acoustic Sensor |
title_fullStr | Evaluating Inhibition of the Epidermal Growth Factor (EGF)-Induced Response of Mutant MCF10A Cells with an Acoustic Sensor |
title_full_unstemmed | Evaluating Inhibition of the Epidermal Growth Factor (EGF)-Induced Response of Mutant MCF10A Cells with an Acoustic Sensor |
title_short | Evaluating Inhibition of the Epidermal Growth Factor (EGF)-Induced Response of Mutant MCF10A Cells with an Acoustic Sensor |
title_sort | evaluating inhibition of the epidermal growth factor (egf)-induced response of mutant mcf10a cells with an acoustic sensor |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263556/ https://www.ncbi.nlm.nih.gov/pubmed/25586035 http://dx.doi.org/10.3390/bios2040448 |
work_keys_str_mv | AT garciamarcelap evaluatinginhibitionoftheepidermalgrowthfactoregfinducedresponseofmutantmcf10acellswithanacousticsensor AT shahidammar evaluatinginhibitionoftheepidermalgrowthfactoregfinducedresponseofmutantmcf10acellswithanacousticsensor AT chenjennifery evaluatinginhibitionoftheepidermalgrowthfactoregfinducedresponseofmutantmcf10acellswithanacousticsensor AT xijun evaluatinginhibitionoftheepidermalgrowthfactoregfinducedresponseofmutantmcf10acellswithanacousticsensor |