Abstract
We present a novel study on label-free recognition and distinction of drug resistant breast cancer cells (MCF-7 DOX) from their parental cells (MCF-7 WT) via impedimetric measurements. Drug resistant cells exhibited significant differences in their dielectric properties compared to wild-type cells, exerting much higher extracellular resistance (Rextra). Immunostaining revealed that MCF-7 DOX cells gained a much denser F-actin network upon acquiring drug resistance indicating that remodeling of actin cytoskeleton is probably the reason behind higher Rextra, providing stronger cell architecture. Moreover, having exposed both cell types to doxorubicin, we were able to distinguish these two phenotypes based on their substantially different drug response. Interestingly, impedimetric measurements identified a concentration-dependent and reversible increase in cell stiffness in the presence of low non-lethal drug doses. Combined with a profound frequency analysis, these findings enabled distinguishing distinct cellular responses during drug exposure within four concentration ranges without using any labeling. Overall, this study highlights the possibility to differentiate drug resistant phenotypes from their parental cells and to assess their drug response by using microelectrodes, offering direct, real-time and noninvasive measurements of cell dependent parameters under drug exposure, hence providing a promising step for personalized medicine applications such as evaluation of the disease progress and optimization of the drug treatment of a patient during chemotherapy.
Highlights
Breast cancer is the most common cancer type in women and one of the leading causes of female mortality worldwide [1]
We investigated whether doxorubicin resistant MCF-7 cells (MCF-7 DOX) can be singled out from their parental cells (MCF7 WT) or not based on their dielectric properties
MCF-7 DOX cells exhibited 50% increase in Rextra compared to MCF-7 WT cells when both were cultured at confluency on platinum electrodes
Summary
Breast cancer is the most common cancer type in women and one of the leading causes of female mortality worldwide [1]. Chemotherapy is still one of the main treatment methods in clinic, causing cell death in breast tumors treated with various anticancer drugs. Despite the fact that many tumors initially respond to chemotherapy, cells can gain resistance and they can adapt to survive. Drug resistance often involves the transition of cancer cells from an anti-estrogen-sensitive, non-metastatic, hormone dependent phenotype to an anti-estrogen-insensitive, metastatic and hormone independent phenotype [2]. Despite the fact that there have been a plethora of studies addressing the mechanism behind drug resistance [3,4,5,6,7,8,9,10,11], a comprehensive answer to such a complex problem still remains elusive. A pressing demand has directed researchers towards the development of rapid and simple techniques for the investigation of interactions of cancer cells with drugs [12] at different stages of the disease
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