The New Application of Real-time Cell-monitoring Analysis System to Detect Cellular Responses in Human Umbilical Vein Endothelial to Paclitaxel

Abstract

Although widely used in the treatment of common cancers, paclitaxel causes angialgia/ phlebitis in 60-70% of patients when administered intravenously to the upper extremities. However, useful laboratory models for the study of angialgia and phlebitis are currently lacking. The purpose of this study was to establish a new application of the real-time cellmonitoring analysis (RTCA) system to detect responses of human umbilical vein endothelial cells (HUVECs) to paclitaxel. We examined the possibility of applying this method to detect the risk of developing angialgia/phlebitis as a side effect of anticancer reagents. HUVECs were seeded onto an E-plate. After 24 h of culture, paclitaxel and carboplatin were added to each well and changes in electrical impedance were then recorded for 72 h. Electrical impedance, outputted as cell index (CI) values, enabled the time-dependent monitoring of the effects of chemotherapeutics on HUVEC viability. Paclitaxel caused a greater concentration-and timedependent decrease in HUVEC CI values than with carboplatin. These findings agree with clinical case data showing that taxanes cause angialgia/phlebitis more frequently than platinum therapies. Furthermore, CI values correlated with increased levels of the inflammatory markers intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and phospho-nuclear factor (P-NF)-κB. Together, these data suggest that our RTCA-based experimental method provides a useful in vitro model for the study of chemotherapy-induced angialgia/phlebitis.

Progress in Research on the Mechanisms and Interventions of Phlebitis from the Perspective of Vascular Endothelial Cell and Signaling Pathway

“…Hazekawa and colleagues applied a real-time cell analyzer (RTCA) system to determine the responses of HUVECs to paclitaxel. 20 After culture of HUVECs in an E-plate for 24 h, paclitaxel and carboplatin were injected into each well and impedance changes were documented for 72 h. The effects of chemotherapeutic agents on HUVEC viability were easily monitored in a time-dependent manner by cell index (CI) values calculated from electrical impedance. Paclitaxel could cause a more obvious decrease in the CI values than carboplatin in a concentration- and time-dependent manner.…”