Evaluating Inhibition of the Epidermal Growth Factor (EGF)-Induced Response of Mutant MCF10A Cells with an Acoustic Sensor

Biosensors

Marcela P. Garcia¹  Ammar Shahid²  Jennifer Y. Chen¹ 

[1] Department of Chemistry, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, USA; E-Mails:;Department of Biology, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, USA; E-Mail:

关键词: QCM-D;    biosensors;    label free;    EGFR;    cell adhesion;    cell signaling;    cytoskeleton;    inhibition;    cancer development;    drug screening;   

DOI  :  10.3390/bios2040448

来源: mdpi

【 摘 要 】

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 IC₅₀ 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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.