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.

• Authors: Weilong Zhong, Wendong Yang, Yuan Qin, Wenguang Gu, Yinyin Xue, Yuanhao Tang, Hengwei Xu, Hongzhi Wang, Chao Zhang, Changhua Wang, Bo Sun, Yanrong Liu, Huijuan Liu, Honggang Zhou, Shuang Chen, Tao Sun, Cheng Yang
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 38 Issue 1 Pg. 285 (Jul 02 2019) ISSN: 1756-9966 [Electronic] England
• PMID: 31266540 (Publication Type: Journal Article)

Chemical References

• Antigens, CD
• Cadherins
• Catechols
• Fatty Alcohols
• Vascular Endothelial Growth Factor A
• beta Catenin
• cadherin 5
• gingerol

Topics

• Animals
• Antigens, CD (metabolism)
• Cadherins (metabolism)
• Catechols (pharmacology, therapeutic use)
• Fatty Alcohols (pharmacology, therapeutic use)
• Female
• Genes, Tumor Suppressor (drug effects)
• Zingiber officinale (chemistry)
• Humans
• Mice
• Mice, Nude
• Microvessels (drug effects)
• Vascular Endothelial Growth Factor A (metabolism)
• beta Catenin (metabolism)