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黄芩苷通过抑制转化生长因子-β1诱导的上皮-间质转化来抑制人骨肉瘤细胞的侵袭、转移和失巢凋亡抗性。

Baicalin inhibits human osteosarcoma cells invasion, metastasis, and anoikis resistance by suppressing the transforming growth factor-β1-induced epithelial-to-mesenchymal transition.

作者信息

Wang Yanmao, Wang Huimin, Zhou Runhua, Zhong Wanrun, Lu Shengdi, Ma Zhongliang, Chai Yimin

机构信息

aDepartment of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital bSchool of Life Sciences, Shanghai University, Shanghai, People's Republic of China.

出版信息

Anticancer Drugs. 2017 Jul;28(6):581-587. doi: 10.1097/CAD.0000000000000495.

Abstract

The epithelial-mesenchymal transition (EMT) plays an important role in inducing cancer metastasis. Baicalin, a flavone derivative isolated from Scutellaria spp., shows a series of pharmacological and physiological activities. However, the possible role of baicalin in the EMT is unclear. In this study, we attempted to investigate the potential use of baicalin as an inhibitor of transforming growth factor-β1 (TGF-β1)-induced EMT in U2OS cells. We found that TGF-β1 induced the EMT to promote U2OS cells migration, invasion, and anoikis resistance. Western blotting showed that baicalin inhibited U2OS cells' invasion and migration, increased the expression of the epithelial phenotype marker E-cadherin, repressed the expression of the mesenchymal phenotype marker vimentin, as well as decreased the level of EMT-inducing transcription factors Snail1 and Slug during the initiation of TGF-β1-induced EMT. Baicalin also inhibited the TGF-β1-induced increase in cell migration, invasion, and anoikis resistance in TGF-β1-induced U2OS cells. In addition, the TGF-β1-mediated phosphorylated levels of Smad2/3 were inhibited by baicalin pretreatment. Above all, we conclude that baicalin suppresses human osteosarcoma cells' migration, invasion, and anoikis resistance in vitro through suppression of TGF-β1-induced EMT.

摘要

上皮-间质转化(EMT)在诱导癌症转移中起重要作用。黄芩苷是从黄芩属植物中分离出的一种黄酮衍生物,具有一系列药理和生理活性。然而,黄芩苷在EMT中的潜在作用尚不清楚。在本研究中,我们试图探究黄芩苷作为转化生长因子-β1(TGF-β1)诱导的U2OS细胞上皮-间质转化抑制剂的潜在用途。我们发现TGF-β1诱导上皮-间质转化以促进U2OS细胞迁移、侵袭和抗失巢凋亡。蛋白质免疫印迹法显示,黄芩苷抑制U2OS细胞的侵袭和迁移,增加上皮表型标志物E-钙黏蛋白的表达,抑制间质表型标志物波形蛋白的表达,并且在TGF-β1诱导上皮-间质转化起始过程中降低上皮-间质转化诱导转录因子Snail1和Slug的水平。黄芩苷还抑制TGF-β1诱导的U2OS细胞迁移、侵袭及抗失巢凋亡能力的增强。此外,黄芩苷预处理可抑制TGF-β1介导的Smad2/3磷酸化水平。综上所述,我们得出结论,黄芩苷通过抑制TGF-β1诱导的上皮-间质转化,在体外抑制人骨肉瘤细胞的迁移、侵袭和抗失巢凋亡能力。

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