6-Gingerol stabilized the p-VEGFR2/VE-cadherin/-catenin/actin complex promotes microvessel normalization and suppresses tumor progression
6-Gingerol stabilized the p-VEGFR2/VE-cadherin/-catenin/actin complex promotes microvessel normalization and suppresses tumor progression
复制标题
6-姜酚稳定 p-VEGFR2/VE-钙粘蛋白/-连环蛋白/肌动蛋白复合物，促进微血管正常化并抑制肿瘤进展
DOI：
10.1186/s13046-019-1291-z
复制
发表时间：
2019-07-02
影响因子：
11.3
通讯作者：
Yang, Cheng
中科院分区：
文献类型：
--
作者：
Zhong, Weilong;Yang, Wendong;Yang, Cheng
背景抗血管生成疗法通过减少肿瘤的血液供应和抑制肿瘤生长而显示出抗肿瘤作用。方法采用CO-IP法、N-STORM法和细胞骨架分析等方法，探讨p-VEGFR 2/VE-cadherin/-catenin/actin复合物调控血管重构、改善肿瘤微环境的机制。6-姜酚（6 G）是生姜中的主要生物活性成分，通过非途径依赖性地增强VEGFa与VEGFR 2的结合来稳定该复合物。Biacore、pull down和分子对接等方法证实了6 G与VEGFR 2的相互作用以及VEGFa与VEGFR 2结合的增强。结果微血管结构熵（MSE）可能是多种肿瘤类型的预后因子，并有可能作为临床生物标志物。6 G调节微血管床的结构组织以通过p-VEGFR 2/VE-钙粘蛋白/β-连环蛋白/肌动蛋白复合物降低MSE并抑制肿瘤进展。6 G促进肿瘤血管的正常化，改善肿瘤微环境，降低MSE，促进化疗药物进入肿瘤核心，从而减少肿瘤的生长和转移。ConclusionsThis study demonstrated the importance of vascular normalization in tumor therapy and elucidated the mechanism of action of ginger，a medical compound that has been used in China since ancient times.
BackgroundAnti-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.MethodsThe CO-IP assays, N-STORM and cytoskeleton analysis were used to confirm the mechanism that p-VEGFR2/VE-cadherin/-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.ResultsHere, 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/-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.ConclusionsThis 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.