2012, 37(5):434-437.
Abstract:Objective:To investigate the antiangiogenic ability and mechanism of Vinorelbine in vitro and in vivo. Methods: In vitro, MTT colorimetric assay was used to observe the effect of Vinorelbine on the proliferation of human umbilical vein endothelial cell (HUVEC) and human pulmonary adenocarcinoma A549 cells. Transwell cabin test and out body canaliculization test were used to observe the impact of Vinorelbine on cell migration and capillary like tube formation ability, and the apoptosis rate of HUVEC was calculated by flow cytometry (FCM). In vivo, the chicken chorioallantoic membrane (CAM) model was used to check whether the neovascularization of CAM could be suppressed. Results: Low dose Vinorelbine (0.1~1.0 ng/ml) could inhibit the proliferation of A549 and HUVEC after 48 h treatment, and the inhibition had significant differences (P=0.000). The number of migrating HUVEC was decreased as compared with that in the control group (P<0.05,F=72.979,P=0.000), and the inhibition rate of migration was between 20/56%~40.40% when treated with 0.1~0.8 ng/ml Vinorelbine for 12 h. The number of tubules was reduced and the lumen lost its integrity as compared with that in the control group (P<0.05,F=75.794,P=0.000), and the inhibition rate of tube formation was between 29.07%~56.83% when treated with 0.1~0.8 ng/ml Vinorelbine for 24 h. When HUVEC was incubated with 0.1~0.8 ng/ml Vinorelbine for 48 h, the apoptosis rate was between 22.30%~37.05%. At the same time, the apoptosis rate was higher than that of 15.60% in the control group (P<0.05); Note: compared with that of the control, P value for 0.1,0.4 ng/ml, and 0.8 ng/ml Vinorelbine was P=0.036, P=0.013, and P=0.012 respectively). We also observed that Vinorelbine, at concentrations of 0.1, 0.4 ng/ml, and 0.8ng/ml, suppressed the neovascularization of CAM in vivo, and the inhibition rate was between 21.05%~42.11%. Moreover, the inhibition rate was enhanced as the drug concentration increased. Conclusion: ① In vitro, low dose Vinorelbine can inhibit the cell proliferation, migration, and tube formation of HUVEC, and has the ability of inducing apoptosis of HUVEC. ② In vivo, low dose Vinorelbine demonstrates antiangiogenic ability of CAM.