Microfluidic chip enables single-cell measurement for multidrug resistance in triple-negative breast cancer cells  

作　　者：Karan Parekh Hamideh Sharifi Noghabi Jose Alejandro Lopez Paul Chi Hang Li 

机构地区：[1]Department of Molecular Biology&Biochemistry,Simon Fraser University,Burnaby V5A 1S6,Canada. [2]Department of Chemistry,Simon Fraser University,Burnaby V5A 1S6,Canada. [3]School of Environment&Science,Griffith University,Nathan,Queensland 4111,Australia.

出　　处：《Cancer Drug Resistance》2020年第3期613-622,共10页癌症耐药（英文）

摘　　要：Aims:Triple-negative breast cancer patients are commonly treated with combination chemotherapy.Nonetheless,outcomes remain substandard with relapses being of a frequent occurrence.Among the several mechanisms that result in treatment failure,multidrug resistance,which is mediated by ATP-binding cassette proteins,is the most common.Regardless of the substantial studies conducted on the heterogeneity of cancer types,only a few assays can distinguish the variability in multidrug resistance activity between individual cells.We aim to develop a single-cell assay to study this.Methods:This experiment utilized a microfluidic chip to measure the drug accumulation in single breast cancer cells in order to understand the inhibition of drug efflux properties.Results:Selection of single cells,loading of drugs,and fluorescence measurement for intracellular drug accumulation were all conducted on a microfluidic chip.As a result,measurements of the accumulation of chemotherapeutic drugs(e.g.,daunorubicin and paclitaxel)in single cells in the presence and absence of cyclosporine A were conducted.Parameters such as initial drug accumulation,signal saturation time,and fold-increase of drug with and without the presence cyclosporine A were also tested.Conclusion:The results display that drug accumulation in a single-cell greatly enhanced over its same-cell control because of inhibition by cyclosporine A.Furthermore,this experiment may provide a platform for future liquid biopsy studies to characterize the multidrug resistance activity at a single-cell level.

关 键 词：MDA-MB-231 cell triple-negative breast cancer microfluidic chip LAB-ON-CHIP multidrug resistance single-cell analysis fluorescence measurement 

分 类 号：R73[医药卫生—肿瘤]