6-Gingerol stabilized the p-VEGFR2/VE-cadherin/β-catenin/actin complex promotes microvessel normalization and suppresses tumor progression
| Autor: | Wen-guang Gu, Yanrong Liu, Honggang Zhou, Shuang Chen, Hongzhi Wang, Bo Sun, Wang Changhua, Tao Sun, Wendong Yang, Weilong Zhong, Yinyin Xue, Yuanhao Tang, Yuan Qin, Heng-Wei Xu, Huijuan Liu, Chao Zhang, Cheng Yang |
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| Rok vydání: | 2019 |
| Předmět: |
Vascular Endothelial Growth Factor A
0301 basic medicine Cancer Research Catechols Mice Nude Ginger lcsh:RC254-282 Metastasis Mice 03 medical and health sciences 0302 clinical medicine Microvascular structural entropy Antigens CD medicine Animals Humans Genes Tumor Suppressor Cytoskeleton Microvessel beta Catenin Tumor microenvironment Chemistry Research lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cadherins medicine.disease Tumor vessel normalization Vascular endothelial growth factor A 030104 developmental biology Oncology Tumor progression 030220 oncology & carcinogenesis Catenin Microvessels Cancer research Female Fatty Alcohols VE-cadherin 6-gingerol |
| Zdroj: | Journal of Experimental & Clinical Cancer Research : CR Journal of Experimental & Clinical Cancer Research, Vol 38, Iss 1, Pp 1-14 (2019) |
| ISSN: | 1756-9966 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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