褐藻苷苔多酚7-Polyphenol-Ecklonia抑制肿瘤转移和血管新生的研究  

Study on the inhibitory effect of 7-Polyphenol-Ecklonia of the brown algae Ecklonia cava on tumor metastasis and angiogenesis

作　　者：杨胜涛 刘怡 萧振邦 黄晓洋 周春霞 千忠吉 YANG Sheng-tao;LIU Yi;XIAO Zhen-bang;HUANG Xiao-yang;ZHOU Chun-xia;QIAN Zhong-ji(College of Food Science and Technology,Guangdong Ocean University,Guangdong Key Laboratory of Aquatic Product Processing and Safety,Guangdong Marine Food Engineering Technology Research Center,Zhanjiang 524088,China;School of Chemistry and Environment,Guangdong Ocean University,Zhanjiang 524088,China;Southern Marine Science and Engineering Guangdong Laboratory,Zhanjiang 524025,China)

机构地区：[1]广东海洋大学食品科技学院,广东省水产品加工与安全重点实验室,广东省海洋食品工程技术研究中心,广东湛江524088 [2]广东海洋大学化学与环境学院,广东湛江524088 [3]南方海洋科学与工程广东省实验室,广东湛江524025

出　　处：《中国海洋药物》2021年第2期35-42,共8页Chinese Journal of Marine Drugs

基　　金：广东省基础与应用基础研究基金项目(2020A1515011075);南方海洋科学与工程重点实验室(湛江)资助项目(ZJW-2019-07);湛江市海洋经济创新发展示范市建设项目(湛海创2017C8B1);广东海洋大学“大学生创新创业训练计划”项目(CXXL2020286)资助。

摘　　要：目的探究海洋褐藻苷苔(Ecklonia cava)多酚7-polyphenol-ecklonia(7PE)对肿瘤侵袭转移和血管生成的影响。方法采用细胞毒性实验检测7PE分别对人成纤维肉瘤细胞(HT-1080)和人脐静脉内皮细胞(HUVEC)的毒性作用;划痕实验检测7PE对HT-1080细胞的迁移能力影响;明胶酶谱法和ELISA检测HT-1080细胞的金属基质蛋白酶-2/9(MMP-2/9)、低氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)蛋白的表达水平;成管实验检测7PE对HUVEC成管的作用;分子对接模拟7PE与MMP-2/9和HIF-1α蛋白的相互作用。结果 7PE明显抑制HT-1080的迁移和MMP-2、MMP-9、VEGF和HIF-1α蛋白的表达;且能明显抑制HUVEC成管能力;此外与MMP-2/9和HIF-1α能形成稳定的相互作用。结论 7PE可抑制肿瘤细胞转移和血管新生,可作为研发抗肿瘤药物的活性物质。Objective To explore the effect of marine brown algae Ecklonia cava polyphenol 7-polyphenol-ecklonia(7 PE) on tumor invasion, metastasis and angiogenesis. Methods Cytotoxicity experiments were used to detect the toxic effects of 7 PE on human fibrosarcoma cells(HT-1080) and human umbilical vein endothelial cells(HUVEC). The scratch test was used to examine the effect of 7 PE on the migration ability of HT-1080 cells. Gelatin zymography and ELISA were used to detect metal matrix proteinase-2/9(MMP-2/9), hypoxia inducible factor-1α(HIF-1α) and vascular endothelial growth factor(VEGF) protein expression level in HT-1080 cells. Tube forming experiment was used to detect the effect of 7 PE on HUVEC tube forming. Molecular docking was used to simulate the interaction of 7 PE with MMP-2/9 and HIF-1α protein, respectively. Results 7 PE obviously inhibited the migration of HT-1080 and the expression of MMP-2/9, VEGF, HIF-1α protein. And 7 PE obviously inhibited the HUVEC tube forming ability. Moreover, it could form stable interaction with MMP-2/9 and HIF-1α. Conclusion 7 PE could inhibit tumor cell metastasis and angiogenesis, and could be used as an active substance in the development of anti-tumor drugs.

关 键 词：褐藻多酚 肿瘤转移 血管新生 金属基质蛋白酶 低氧诱导因子-1Α 

分 类 号：R73-37[医药卫生—肿瘤] R931.77[医药卫生—临床医学]