| Recent years,tumor vessels provide nutrients and oxygen to maintain the growth of tumor and regulate tumor microenvironment.Anti-angiogenic therapy has been designed to reduce angiogenesis and suppress tumor progression.However,large number of research showed that anti-angiogenic agents are often followed side-effect,such as deterioration of tumor microenvironment and lead to tumor progress,increased tumor necrosis and establishment of resistance and escape mechanisms.Reversing the deterioration of tumor microenvironment and weakening the stress of tumor cells can suppress tumor progress.Increased vascular permeability without injury or physical exposure of endothelial,reduce thrombosis and tumor hematogenous metastasis and increase blood supply to tumors,improve tumor microenvironment holding the progressive process of malignant cells.Increase permeability can regulate oxygen partial pressure and distribution of nutrients and oxygen.Then,HIF1a-VEGFa feedback and reduce recruitment of tumor cells or VM formation.Morphologic changes from multi-branches and short-intervals into little-branches and long-intervals of tumor microvasculature networks.In this study,we screened natural molecules with vascular regulatory activity and observed that 6-gingerol can regulate the normalization of tumor blood vessels and further inhibit the progression of the tumor.Further proteomics analysis indicated that 6-gingerol directly targeting and activation VEGFR2.Furthermore,6-gingerol particularly promote VEGFa/VEGFR2 interaction.6-Gingerol dragging the ability to promote angiogenesis of VEGFa/VEGFR1 and rebalance the weighting of VEGFR2/VEGFR1 in tumor angiogenesis.Rebalance of VEGFR2/VEGFR1 changed the permeability of endothelial cells,promote the normalization of tumor micro-circulation networks and improve tumor microenvironment,resulting in inhibiting tumor progress and significantly increased cytotoxic effect of chemotherapy drugs. |
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