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BIOMEDICAL CHROMATOGRAPHY · 2014 ·Vol. 28 ·期 10 ·1393-1401 · IF 1.662

Quantitative study of cellular heterogeneity in doxorubicin uptake and its pharmacological effect on cancer cells

Bin Deng,Zhi-Ming Wang,Zi-Hao Zhou,Yi-Meng Liu,Xi-Liang Yang,Jian Song,Yu-Xiu Xiao

Cellular heterogeneity in doxorubicin (DOX) uptake and its relationship with pharmacological effect on cancer cells were quantitatively investigated for the first time. An in vitro experimental model was established by treating human leukemia K562 and breast cancer MCF-7 cells with different schedules of DOX with or without surface P-glycoprotein (P-gp) inhibitor verapamil (VER). The cellular heterogeneity in DOX uptake was quantitatively examined by single-cell analysis using capillary electrophoresis coupled with laser-induced fluorescence detection. The corresponding cytotoxic effect was tested by cellular morphology, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium and flow cytometry assays. The expression of cellular membrane surface P-gp was determined by flow cytometry. Results showed that the cellular heterogeneity exists in DOX uptake. The single-high DOX schedule leads to lower uptake heterogeneity and higher mean drug uptake. The cellular heterogeneity in DOX uptake was found to be negatively correlated with drug cytotoxicity and surface P-gp expression, with r = −0.7680 to ~ −0.9587. VER reduces the cellular variation in DOX uptake, suggesting that surface P-gp may be one of the causes of the cellular heterogeneity in DOX uptake. This research demonstrates the importance of quantitative study of cellular heterogeneity in drug uptake and its potential application in drug schedule design, response prediction and therapy modulation. Copyright © 2014 John Wiley & Sons, Ltd.

CAS / MDL: 151-21-3
研究领域: 药理学 · 肿瘤学 · 细胞生物学
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iScience · 2023 · IF 5.8

Vertical impedance electrode array for spatiotemporal dynamics monitoring of 3D cells under drug diffusion effect

Yong Qiu,Xin Liu,Yuxuan Zhu,Deming Jiang,Fengheng Li,Weijie Yu,Hao Wan,Liujing Zhuang,Yuxiang Pan,Ping Wang

Although three-dimensional (3D) tumor models feature more accurate responses to drugs, the Matrigel scaffold affects the drug diffusion effect. Obtaining accurate drug spatiotemporal response characteristics is of great significance in the drug screening domain. However, the conventional cell-based sensors are difficult to perform spatiotemporal dynamics impedance monitoring of 3D cells and evaluate the anti-cancer pharmacological effect. Here, we proposed a biosensing platform involving a vertical impedance electrode array (VIEA) chip and a multichannel detection system. The platform can dynamically record 3D cell impedance in the vertical direction, which is consistent with time- and location-dependent drug penetration, closely related to spatiotemporal cell viability under drug effects. The subtle changes of impedance signals in different locations induced by drug diffusion can be detected, which demonstrates its high performance in drug systematic evaluation. The universal and high-content 3D cell biosensing platform is believed to have promising potential in pharmacodynamics investigation and preclinical drug screening.

研究领域: 生物医学工程 · 药学 · 细胞生物学 · 药物发现
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