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 res...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.展开更多
文摘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.
