Carvedilol may attenuate liver cirrhosis by inhibiting angiogenesis through the VEGF-Src-ERK signaling pathway

摘要: AIM: To investigate the effect of carvedilol on angiogenesis and underlying signaling pathways. METHODS: The was examined using a human umbilical vascular endothelial cell (HUVEC) model. viability measured by CCK8 assay. Flow cytometry used to assess cycle progression. Cell migration, transwell migration tube formation assays were performed analyze HUVEC function. Vascular growth factor (VEGF) induced activation HUVECs, which pretreated with different concentrations or none. Western blot analysis detected phosphorylation levels three pathway proteins, VEGFR-2, Src, extracellular signal-regulated kinase (ERK). specific Src inhibitor PP2 role in VEGF-induced angiogenic pathway. RESULTS: Carvedilol inhibited proliferation dose-dependent manner (IC50 = 38.5 mmol/L). distribution cells S phase decreased from 43.6% 37.2%, 35.6% 17.8% 1, 5 10 μmol/L for 24 h, respectively. (10 μmol/L) reduced 67.54 ± 7.83 37.11 3.533 (P < 0.001). invasion 196.3% 18.76% 114.0% 12.20% 51.68% 8.28%, also significantly 286.0 36.72 135.7 18.13 0.05) 80.27 11.16 0.01) We investigated several intracellular protein determine reason these reductions. Treatment tyrosine VEGFR-2 175.5% 8.54% 52.67% 5.33% 0.01). Additionally, ERK 1/2 181.9% 18.61% 56.45% 7.64% increase activity alleviated [decreased 141.8% 15.37% 53.57 7.18% 47.04% 9.74% at μmol/L, respectively]. Pretreatment HUVECs almost completely prevented upregulation 213.2% 27.68% 90.96% 17.16% 0.01)]. CONCLUSION: has an anti-angiogenic HUVECs. This inhibitory is mediated Src-ERK pathways.