6-Gingerol stabilized the p-VEGFR2/VE-cadherin/β-catenin/actin complex promotes microvessel normalization and suppresses tumor progression

Abstract

Background Anti-angiogenic therapies demonstrate anti-tumor effects by decreasing blood supply to tumors and inhibiting tumor growth. However, anti-angiogenic therapy may leads to changes in tumor microenvironment and increased invasiveness of tumor cells, which in turn promotes distant metastasis and increased drug resistance. Methods The CO-IP assays, N-STORM and cytoskeleton analysis were used to confirm the mechanism that p-VEGFR2/VE-cadherin/β-catenin/actin complex regulates vascular remodeling and improves the tumor microenvironment. 6-gingerol (6G), the major bioactive component in ginger, stabilized this complex by enhancing the binding of VEGFa to VEGFR2 with non-pathway dependent. Biacore, pull down and molecular docking were employed to confirm the interaction between 6G and VEGFR2 and enhancement of VEGFa binding to VEGFR2. Results Here, we report that microvascular structural entropy (MSE) may be a prognostic factor in several tumor types and have potential as a biomarker in the clinic. 6G regulates the structural organization of the microvascular bed to decrease MSE via the p-VEGFR2/VE-cadherin/β-catenin/actin complex and inhibit tumor progression. 6G promotes the normalization of tumor vessels, improves the tumor microenvironment and decreases MSE, facilitating the delivery of chemotherapeutic agents into the tumor core and thereby reducing tumor growth and metastasis. Conclusions This study demonstrated the importance of vascular normalization in tumor therapy and elucidated the mechanism of action of ginger, a medicinal compound that has been used in China since ancient times. Electronic supplementary material The online version of this article (10.1186/s13046-019-1291-z) contains supplementary material, which is available to authorized users.

[Retracted] CircANXA2 Promotes Myocardial Apoptosis in Myocardial Ischemia‐Reperfusion Injury via Inhibiting miRNA‐133 Expression

“…Various revascularization methods can alleviate myocardial injury and necrosis caused by ischemia by restoring myocardial perfusion in time and effectively. However, restoration of blood reperfusion after myocardial ischemia can itself further lead to myocardial cell damage and even necrosis, a phenomenon known as myocardial ischemia-reperfusion injury [ 14 – 18 ]. However, up to now, there is still no effective clinical treatment method to avoid myocardial ischemia-reperfusion injury, which seriously restricts the therapeutic effect of coronary heart disease.…”

<p>CircCFL1/MiR-107 Axis Targeting HMGB1 Promotes the Malignant Progression of Diffuse Large B-Cell Lymphoma Tumors</p>

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Solanine Inhibits Immune Escape Mediated by Hepatoma Treg Cells via the TGFβ/Smad Signaling Pathway

“…Hepatocellular carcinoma (HCC) is one of the most common malignancies and ranks the second leading cause of cancer death worldwide [ 24 – 26 ]. Immunotherapy is one of the important means of tumor therapy.…”