| BackgroundSearching for active ingredients of natural products has become one efficient way for drug discovery.It has been found that berberine has a wide range of pharmacological effects,and its application as a lead compound of anti-cancer drugs has been widely reported.Previous studies showed that berberine had a good binding effect with VEGFR2 through reverse virtual screening,which was a critical target-related tumor angiogenesis.Therefore,it is inferred that berberine has the potential of anti-angiogenesis.ObjectiveThis study aimed to investigate the effect of berberine on angiogenesis and the underlying regulation mechanism of signal transduction.MethodsThe potential targets of berberine were reverse screened.The interaction between the compound and target were detected by molecular docking,surface plasmon resonance(SPR),enzyme-activity experiment and western blot assay.MTT assay was used to investigate the effect of berberine on the proliferation of EA.hy926 cells.Migration inhibition experiment,and chick embryo chorioallantoic membrane(CAM)assays were performed on models of angiogenesis.Western blotting assay was evaluated the biological effects of berberine of the related target.ResultsReverse screen and molecular docking results showed a good binding relationship between the berberine and VEGFR2,which was confirmed by SPR analysis.MTT assay,migration experiment results showed a remarkable inhibitive effect against the proliferation and migration of EA.hy926 cells,as well as significant anti-angiogenesis activities in CAM assay.Furthermore,enzyme-activity experiment and western blot assay showed that berberine remarkably inhibited the activity of VEGFR2 and blocked the VEGFR2-mediated Akt/mTOR/p70s6 k signaling pathway in vitro.ConclusionBerberine can be utilized as an anti-cancer drug by targeting the VEGFR2 and VEGFR2-mediated Akt/mTOR/p70s6 k signaling pathway that lead to inhibition of neovessel growth. |
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