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白藜芦醇通过抑制Wnt信号通路抑制子宫肉瘤细胞的增殖并诱导其凋亡。

Resveratrol suppresses proliferation and induces apoptosis of uterine sarcoma cells by inhibiting the Wnt signaling pathway.

作者信息

Mineda Ayuka, Nishimura Masato, Kagawa Tomohiro, Takiguchi Eri, Kawakita Takako, Abe Akiko, Irahara Minoru

机构信息

Department of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan.

出版信息

Exp Ther Med. 2019 Mar;17(3):2242-2246. doi: 10.3892/etm.2019.7209. Epub 2019 Jan 28.

Abstract

Resveratrol, a natural product and peroxisome proliferator-activated receptor (PPAR) agonist, has been reported to exert anti-cancer effects in several tumor models. A previous study by our group reported that prostaglandin J2, a PPARγ ligand, inhibited cell proliferation in a uterine sarcoma cell line. The aim of the present study was to investigate the role of the Wnt signaling pathway in resveratrol-induced apoptosis and inhibition of cell proliferation in the MES-SA human uterine sarcoma cell line. A WST-1 assay demonstrated that resveratrol inhibited cell proliferation in the MES-SA cell line, and flow cytometry revealed that the number of apoptotic cells increased in a resveratrol dose-dependent manner. The mechanisms underlying these effects of resveratrol were speculated to involve the expression of β-catenin and its target gene, c-myc, which were examined using western blot analysis. The results revealed a dose-dependent downregulation of this β-catenin and c-myc. This effect was blunted by a pharmacological inhibitor of glycogen synthase kinase 3β. Therefore, it is likely that resveratrol inhibited the cell proliferation and increased the number of apoptotic cells, at least partially, via the Wnt signaling pathway. The present results suggest that resveratrol is a potential candidate for the treatment of uterine sarcoma.

摘要

白藜芦醇是一种天然产物和过氧化物酶体增殖物激活受体(PPAR)激动剂,据报道在多种肿瘤模型中具有抗癌作用。我们小组之前的一项研究报告称,PPARγ配体前列腺素J2可抑制子宫肉瘤细胞系中的细胞增殖。本研究的目的是探讨Wnt信号通路在白藜芦醇诱导的MES-SA人子宫肉瘤细胞系凋亡和细胞增殖抑制中的作用。WST-1检测表明白藜芦醇可抑制MES-SA细胞系中的细胞增殖,流式细胞术显示凋亡细胞数量以白藜芦醇剂量依赖性方式增加。推测白藜芦醇这些作用的机制涉及β-连环蛋白及其靶基因c-myc的表达,通过蛋白质印迹分析对其进行检测。结果显示β-连环蛋白和c-myc呈剂量依赖性下调。糖原合酶激酶3β的药理学抑制剂可减弱这种作用。因此,白藜芦醇可能至少部分通过Wnt信号通路抑制细胞增殖并增加凋亡细胞数量。目前的结果表明白藜芦醇是治疗子宫肉瘤的潜在候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d490/6396019/0aabd6c4e5ca/etm-17-03-2242-g00.jpg

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