title: Involvement of Toll-like receptor 4 in vinorelbine-induced vascular endothelial injury.
abstract: Vinorelbine (VIN) is a semi-synthetic vinca alkaloid and is one of the most active agents for the treatment of solid tumors. The drug is commonly administered through a peripheral vein. Although VIN is known to cause local venous toxicity, such as drug-induced phlebitis, the mechanism responsible for the toxicity remains unclear. To investigate the role of Toll-like receptor 4 (TLR4) in VIN-induced vascular endothelial injury, human umbilical vein endothelial cells (HUVECs) were prepared from umbilical cords recovered with the written informed consent of the parents and treated with VIN for 60 min. Following the washing away of the VIN, the cells were cultured for a further 6 and 12 h, and the changes in TLR4 expression in the HUVECs were detected by quantitative polymerase chain reaction and western blot analyses. Finally, the effects of VIN on the translocation of nuclear factor κB (NF-κB) were determined by immunofluorescence and confocal analysis. The VIN-treated cells were stretched, extended and irregular while the control cells exhibited normal morphology. The TLR4 mRNA and protein levels were significantly higher in the VIN-treated HUVECs than those in the control group (P<0.05). The rate of NF-κB p65 nuclear translocation in the VIN-treated HUVECs was significantly higher than that in the vehicle-treated group (P<0.05). These results indicated that TLR4 is involved in the development of VIN-induced vascular endothelial injury by affecting the translocation of NF-κB.
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Qian
authors.affiliation: School of Nursing, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.affiliation: School of Nursing, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
keywords: Toll-like receptor 4; human umbilical vein endothelial cell; vinorelbine