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松果菊苷通过抑制 Wnt/β-catenin 信号通路抑制乳腺癌细胞。

Echinacoside inhibits breast cancer cells by suppressing the Wnt/β-catenin signaling pathway.

机构信息

Department of Forensic Medicine, Chongqing Medical University, Chongqing, 400016, China.

Forensic Identification Center, College of Criminal Investigation, Southwest University of Political Science and Law, Chongqing, 401120, China.

出版信息

Biochem Biophys Res Commun. 2020 May 21;526(1):170-175. doi: 10.1016/j.bbrc.2020.03.050. Epub 2020 Mar 20.

Abstract

Echinacoside, a small molecule derived from the natural herbs Cistanche and Echinacea, shows effective anticancer abilities, but the mechanism remains unclear. By using colony formation, scratch, and transwell assays in MDA-MB-231 breast cancer cells, we confirmed the anti-breast cancer ability of Echinacoside in vitro. In addition, we found that Echinacoside can dose-dependently reduce phosho-LRP6, total LRP6, phosho-Dvl2, active β-catenin, and total β-catenin protein expression level in MDA-MB-231 and MDA-MB-468 cells by western blot. We also detected well-known Wnt targets genes, including LEF1, CD44, and cyclin D1 by real-time PCR and western blot, and Echinacoside significantly shows inhibition effect in these two breast cancer cell lines. Furthermore, we investigated its anti-breast cancer ability in an MDA-MB-231 xenograft model in vivo. Echinacoside treatment significantly reduced tumor growth, which was accompanied by a reduction in Wnt/β-catenin signaling. In summary, our results demonstrate that Echinacoside can effectively inhibit Wnt/β-catenin signaling, and therefore, it may be a promising therapeutic target to treat breast cancer.

摘要

松果菊苷是一种从肉苁蓉和紫锥菊等天然草药中提取的小分子,具有有效的抗癌能力,但具体机制尚不清楚。通过在 MDA-MB-231 乳腺癌细胞中进行集落形成、划痕和 Transwell 测定,我们在体外证实了松果菊苷的抗乳腺癌能力。此外,我们发现松果菊苷通过 Western blot 可剂量依赖性降低 MDA-MB-231 和 MDA-MB-468 细胞中磷酸化 LRP6、总 LRP6、磷酸化 Dvl2、活性 β-连环蛋白和总 β-连环蛋白的蛋白表达水平。我们还通过实时 PCR 和 Western blot 检测了 Wnt 信号通路的已知靶基因,包括 LEF1、CD44 和 cyclin D1,松果菊苷在这两种乳腺癌细胞系中均表现出明显的抑制作用。此外,我们在体内 MDA-MB-231 异种移植模型中研究了其抗乳腺癌能力。松果菊苷治疗可显著抑制肿瘤生长,同时伴随 Wnt/β-连环蛋白信号通路的下调。综上所述,我们的研究结果表明,松果菊苷可有效抑制 Wnt/β-连环蛋白信号通路,因此,它可能是治疗乳腺癌的一种有前途的治疗靶点。

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