| Bioelectrical impedance essentially reflects the physical changes related to tissue physiology and pathology.Homeostasis in the human body is strictly regulated.The environment of diseased tissue is destroyed,which leads to the change of physical properties.Studies have shown that bioelectrical impedance can effectively distinguish the different pathological stages of breast cancer tissues,and developed a noninvasive detection method represented by electrical impedance imaging,which has attracted the attention of researchers.This paper aims to study the correlation between breast cancer electrical conductivity and several well-known biomarkers,and explore the regulatory mechanism of electrical conductivity changes in breast cancer.In order to detect the difference of conductivity at the cell level,this paper proposed and established a cell suspension conductivity measurement object with cell growth medium as the solvent.By measuring the conductivity of cell growth medium,cell and cell suspension,it was found that the conductivity of MDA-MB-231 cell suspension with strong metastasis of breast cancer was more affected by the conductivity of cell growth medium than cell conductivity.The change of cell suspension conductivity was consistent with that of tissue samples.The results show that the establishment of cell suspension measurement object with cell growth medium as solvent is more suitable for the study of breast cancer conductivity at the cell level.From the perspective of tumor characteristics,this paper analyzed the correlation between the life activities that affect the ion concentration and the change of electrical conductivity in the process of breast cancer cell development.By detecting the markers of proliferation(Ki67,cyclingd1),migration(MIIP,mobility),abnormal metabolism(ldhA,lactic acid),acidity(NHE1,ΔpH)and hypoxia microenvironment(HIF-1α)in breast cancer tissues and cells at different stages,the correlation between the markers and the conductivity of breast cancer tissues and cells at different stages was analyzed.The results showed that the proliferation,migration,metabolic abnormalities,acidic and hypoxic microenvironment of breast cancer tissue and cells were significantly correlated with the electrical conductivity of breast cancer tissue and cell suspension,and the expression of NHE1 was the most relevant biomarker.From the perspective of electrolytes,it was proved that the electrical conductivity of breast cancer is significantly related to the occurrence and development of tumor.According to the characteristics of tumor angiogenesis,the correlation between angiogenesis and the change of electrical conductivity in the development of breast cancer was analyzed.By detecting the angiogenesis of breast cancer tissue in different periods,the correlation between the conductivity of breast cancer tissue and angiogenesis was analyzed.By detecting the different processes of angiogenesis mediated by VEGFA in breast cancer cells at different stages,the correlation between the electrical conductivity of breast cancer cells at different stages was analyzed.Objective to improve the correlation between breast cancer electrical conductivity and biomarkers affecting water content.The results showed that the conductivity of breast cancer tissue was significantly correlated with angiogenesis.The different processes of angiogenesis mediated by VEGFA were also significantly correlated with the conductivity of breast cancer cell suspension.Among them,VEGFA mediated HUVECs proliferation was most significantly correlated with cell suspension conductivity.From the point of view of water content,the electrical conductivity of breast cancer is significantly correlated with the occurrence and development of tumor.In order to explore the key proteins and signaling pathways regulating the change of electrical conductivity,we found that NHE1 had the strongest correlation with the electrical conductivity of breast cancer cell suspension and tissue,and used different inhibitors to regulate the expression of different proteins.The results showed that Akt and ERK pathway could regulate the change of electrical conductivity by regulating NHE1,and NHE1 could change the extracellular pH and electrical conductivity by controlling ion transport.These results suggest that NHE1 plays a key regulatory role in the process of electrical conductivity changes in breast cancer.In conclusion,we established a new measurement object of cell suspension conductivity,and analyzed the correlation between physiological activity markers of breast cancer and conductivity.Moreover,NHE1,which has the strongest correlation,was used to obtain the related pathway regulating the conductivity of breast cancer cells for the first time.It lays a foundation for the study of the biological mechanism of electrical conductivity change,and further provides a biological basis for promoting the clinical application of the detection technology characterized by electrical conductivity. |
PDF Full Text Request