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Inhibition of TGF-β Signaling in Gliomas by the Flavonoid Diosmetin Isolated from Dracocephalum peregrinum L.

机译:百日草中黄酮类薯Di皂素对胶质瘤中TGF-β信号的抑制作用。

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摘要

L., a traditional Kazakh medicine, has good expectorant, anti-cough, and to some degree, anti-asthmatic effects. Diosmetin (3′,5,7-trihydroxy-4′-methoxyflavone), a natural flavonoid found in traditional Chinese herbs, is the main flavonoid in L. and has been used in various medicinal products because of its anticancer, antimicrobial, antioxidant, estrogenic, and anti-inflammatory effects. The present study aimed to investigate the effects of diosmetin on the proliferation, invasion, and migration of glioma cells, as well as the possible underlying mechanisms. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), scratch wound, and Transwell assays were used to demonstrate the effects of diosmetin in glioma. Protein levels of Bcl-2, Bax, cleaved caspase-3, transforming growth factor-β (TGF-β), E-cadherin, and phosphorylated and unphosphorylated smad2 and smad3 were determined by Western blots. U251 glioma cell development and progression were measured in vivo in a mouse model. Diosmetin inhibited U251 cell proliferation, migration, and invasion in vitro, the TGF-β signaling pathway, and Bcl-2 expression. In contrast, there was a significant increase in E-cadherin, Bax, and cleaved caspase-3 expression. Furthermore, it effectively reduced the tumorigenicity of glioma cells and promoted apoptosis in vivo. The results of this study suggest that diosmetin suppresses the growth of glioma cells in vitro and in vivo, possibly by activating E-cadherin expression and inhibiting the TGF-β signaling pathway.
机译:L.是哈萨克斯坦的传统药物,具有很好的祛痰,抗咳嗽和一定程度的抗哮喘作用。薯met皂素(3',5,7-三羟基-4'-甲氧基黄酮)是中草药中的天然类黄酮,是左旋糖苷的主要黄酮,由于其抗癌,抗微生物,抗氧化剂,雌激素和抗炎作用。本研究旨在研究薯os皂素对神经胶质瘤细胞增殖,侵袭和迁移的影响,以及可能的潜在机制。使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物(MTT),刮擦伤口和Transwell分析法来证明Diosmetin在神经胶质瘤中的作用。通过蛋白质印迹法测定Bcl-2,Bax,裂解的caspase-3,转化生长因子-β(TGF-β),E-cadherin以及磷酸化和未磷酸化的smad2和smad3的蛋白水平。在小鼠模型中体内测量了U251神经胶质瘤细胞的发育和进程。在体外,Diosmetin抑制U251细胞的增殖,迁移和侵袭,TGF-β信号通路和Bcl-2表达。相反,E-cadherin,Bax和裂解的caspase-3表达显着增加。此外,它有效地降低了神经胶质瘤细胞的致瘤性,并促进了体内的细胞凋亡。这项研究的结果表明,薯os皂素可能通过激活E-钙黏着蛋白表达并抑制TGF-β信号通路来抑制神经胶质瘤细胞的体外和体内生长。

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