Assessing Cytotoxic Effect of ZD6474 on MDA-MB-468 Cells Using Cell-Based Sensor | IEEE Journals & Magazine | IEEE Xplore

Assessing Cytotoxic Effect of ZD6474 on MDA-MB-468 Cells Using Cell-Based Sensor


Abstract:

This paper presents the application of an impedance-based measurement of cytotoxicity of ZD6474 on MDA-MB-468 breast cancer cells in culture. In the present experiment, f...Show More

Abstract:

This paper presents the application of an impedance-based measurement of cytotoxicity of ZD6474 on MDA-MB-468 breast cancer cells in culture. In the present experiment, four types of cell-based sensors with different electrode geometries are fabricated by using microfabrication technology. MDA-MB-468 cells are grown on the electrode surfaces to study cell adhesion, spreading, and apoptosis. The real time impedance monitoring data show that the cells took to complete the spreading process on electrode surfaces. The cytotoxic effect of ZD6474 is dose dependant and with the increases of drug doses, the impedance value decreases, which correlates that ZD6474 blocks cell proliferation and induces apoptosis in breast cancer cells. A quantitative relationship, developed between the impedance and drug doses, establishes a negative correlation between the drug doses and impedance. General consistency has been found between the impedance response and the biochemical assay. Thus, impedance sensing method provides a simple and cost effective method to study chemical cytotoxicity in vitro.
Published in: IEEE Sensors Journal ( Volume: 14, Issue: 5, May 2014)
Page(s): 1476 - 1481
Date of Publication: 02 January 2014

ISSN Information:


I. Introduction

In VITRO cytotoxicity assays are used for several decades to study the effects of certain chemicals on cells in culture. These cell-based assays play major alternative methods to animal testing for cytotoxicity assessment of several chemicals and drugs and help to speed up the process of new drug discovery. The cell motility after exposure to a drug was studied by several conventional in vitro cell-based assays such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test (MTT assay), neutral red uptake, colony forming efficiency or phase contrast imaging [1]. However, most of these assays detect only specific cellular changes and do not give information about cell-drug interaction. Moreover, these assays are time and labor consuming, and require complex steps. Therefore, at this stage of advanced cell and molecular biology research we need label-free detection methods for cell-based assays. Monitoring the bioimpedance properties of cells using cell based sensor is one of the non-labeling techniques used to understand the cell functionality on electrode surfaces. The cell based sensor is also being explored for continuous, automatic, and real time monitoring of cell adhesion and spreading as well as cell motility induced by drug. Cell based sensors have been successfully used to study the cytotoxicity of several drugs [1]–[8]. In this paper, electrical properties of cells are studied in the presence of anticancer drug to understand the changes in different physiological conditions. ZD6474 has more potential to combat breast cancer among the recently discovered anticancer drugs. ZD6474 is a novel heteroaromatic-substituted anilinoquinazoline, which acts as a reversible inhibitor of Adenosine tri phosphate (ATP) [9]. The inhibitory effect of ZD6474 on epidermal growth factor receptor (EGFR) tyrosine kinase was already reported [10]. ZD6474 inhibits two key pathways in tumour growth by inhibiting VEGF-dependent tumour angiogenesis along with VEGF-dependent endothelial cell survival [11]–[14], and also by inhibiting EGFR-dependent tumour cell proliferation [15]. However the impedimetric real time monitoring of cytotoxicty of ZD6474 on MDA-MB-468 has not been carried out till date. The purpose of this study is to understand cell responses subjected to various drug doses using miniature cell based sensors. This study provides results about real time monitoring of cell adhesion, proliferation, and cell mortality of MDA-MB-468 cells cultured in microfabricated sensors using electric cell-substrate impedance sensing (ECIS) technique. Subsequently the frequency response of electrical impedance of ZD6474 drug treated MDA-MB-468 cells is investigated and the results are correlated with the results of conventional technique like MTT assay. Further, quantitative estimation of the effect of drug dose on the cells is also assessed using impedance data.

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References

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