OBJECTIVE To evaluate the effect of Guizhi Fuling Capsule active pharmaceutical ingredient(API)and its fractions on human breast cancer cells proliferation by high-throughput screening assay.METHODS The crude fraction...OBJECTIVE To evaluate the effect of Guizhi Fuling Capsule active pharmaceutical ingredient(API)and its fractions on human breast cancer cells proliferation by high-throughput screening assay.METHODS The crude fractions were obtained from the extraction and elution of the API of Guizhi Fuling Capsule,and 929 standard fractions were obtained by the optimal separation conditions.Sulforhodamine B(SRB)method was used to evaluate the effects of the Guizhi Fuling capsule API and929 kinds of fractions on the proliferation of human breast cancer cells MCF-7 and MDA-MB-231.RESULTS The Guizhi Fuling capsule API had a strong ability to inhibit the proliferation of MCF-7 cells at high concentration and the ability to inhibit MDA-MB-231 cells' proliferate at low concentration following 72 h treatment;some samples of 929 fractions(5μg·mL^(-1))was found to have a breast cancer cell growth inhibition rate above 50%,without toxicity on HUVECs proliferation.CONCLUSION The API of Guizhi Fuling capsule had significant cytotoxicity effects on these two human breast cancer cells,with significant concentration-and time-dependent manner.展开更多
The process of in situ tumors developing into malignant tumors and exhibiting invasive behavior is extremely complicated.From a biophysical point of view,it is a phase change process affected by many factors,including...The process of in situ tumors developing into malignant tumors and exhibiting invasive behavior is extremely complicated.From a biophysical point of view,it is a phase change process affected by many factors,including cell-to-cell,cell-to-chemical material,cell-to-environment interaction,etc.In this study,we constructed spheroids based on green fluorescence metastatic breast cancer cells MDA-MB-231 to simulate malignant tumors in vitro,while constructed a three-dimensional(3D)biochip to simulate a micro-environment for the growth and invasion of spheroids.In the experiment,the 3D spheroid was implanted into the chip,and the oriented collagen fibers controlled by collagen concentration and injection rate could guide the MDA-MB-231 cells in the spheroid to undergo directional invasion.The experiment showed that the oriented fibers greatly accelerated the invasion speed of MDA-MB-231 cells compared with the traditional uniform tumor micro-environment,namely obvious invasive branches appeared on the spheroids within 24 hours.In order to analyze this interesting phenomenon,we have developed a quantitative analyzing approach to explore strong angle correlation between the orientation of collagen fibers and invasive direction of cancer cell.The results showed that the oriented collagen fibers produced by the chip can greatly stimulate the invasion potential of cancer cells.This biochip is not only conducive to modeling cancer cell metastasis and studying cell invasion mechanisms,but also has the potential to build a quantitative evaluation platform that can be used in future chemical drug treatments.展开更多
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
基金supported by National Science and Technology Major Projects of China(2013ZX09402203,2013ZX09508104)Medical and Health Science and Technology Innovation Engineering of Chinese Academy of Medical Sciences(2016-I2M-3-007)National Natural Science Foundation of China(81573454)
文摘OBJECTIVE To evaluate the effect of Guizhi Fuling Capsule active pharmaceutical ingredient(API)and its fractions on human breast cancer cells proliferation by high-throughput screening assay.METHODS The crude fractions were obtained from the extraction and elution of the API of Guizhi Fuling Capsule,and 929 standard fractions were obtained by the optimal separation conditions.Sulforhodamine B(SRB)method was used to evaluate the effects of the Guizhi Fuling capsule API and929 kinds of fractions on the proliferation of human breast cancer cells MCF-7 and MDA-MB-231.RESULTS The Guizhi Fuling capsule API had a strong ability to inhibit the proliferation of MCF-7 cells at high concentration and the ability to inhibit MDA-MB-231 cells' proliferate at low concentration following 72 h treatment;some samples of 929 fractions(5μg·mL^(-1))was found to have a breast cancer cell growth inhibition rate above 50%,without toxicity on HUVECs proliferation.CONCLUSION The API of Guizhi Fuling capsule had significant cytotoxicity effects on these two human breast cancer cells,with significant concentration-and time-dependent manner.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11974066 and 11674043)the Fundamental Research Funds for the Central Universities,China(Grant No.2019CDYGYB007)the Natural Science Foundation of Chongqing,China(Grant No.cstc2019jcyj-msxmX0477).
文摘The process of in situ tumors developing into malignant tumors and exhibiting invasive behavior is extremely complicated.From a biophysical point of view,it is a phase change process affected by many factors,including cell-to-cell,cell-to-chemical material,cell-to-environment interaction,etc.In this study,we constructed spheroids based on green fluorescence metastatic breast cancer cells MDA-MB-231 to simulate malignant tumors in vitro,while constructed a three-dimensional(3D)biochip to simulate a micro-environment for the growth and invasion of spheroids.In the experiment,the 3D spheroid was implanted into the chip,and the oriented collagen fibers controlled by collagen concentration and injection rate could guide the MDA-MB-231 cells in the spheroid to undergo directional invasion.The experiment showed that the oriented fibers greatly accelerated the invasion speed of MDA-MB-231 cells compared with the traditional uniform tumor micro-environment,namely obvious invasive branches appeared on the spheroids within 24 hours.In order to analyze this interesting phenomenon,we have developed a quantitative analyzing approach to explore strong angle correlation between the orientation of collagen fibers and invasive direction of cancer cell.The results showed that the oriented collagen fibers produced by the chip can greatly stimulate the invasion potential of cancer cells.This biochip is not only conducive to modeling cancer cell metastasis and studying cell invasion mechanisms,but also has the potential to build a quantitative evaluation platform that can be used in future chemical drug treatments.
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.
