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槲皮素可抑制上皮-间质转化,降低侵袭性和转移能力,并通过抑制胰腺癌细胞中的信号转导和转录激活因子3(STAT3)信号传导,逆转白细胞介素-6(IL-6)诱导的上皮-间质转化及基质金属蛋白酶(MMP)的表达。

Quercetin inhibits epithelial-mesenchymal transition, decreases invasiveness and metastasis, and reverses IL-6 induced epithelial-mesenchymal transition, expression of MMP by inhibiting STAT3 signaling in pancreatic cancer cells.

作者信息

Yu Dinglai, Ye Tingting, Xiang Yukai, Shi Zhehao, Zhang Jie, Lou Bin, Zhang Fan, Chen Bicheng, Zhou Mengtao

机构信息

Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, People's Republic of China.

Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Wenzhou, Zhejiang Province, People's Republic of China.

出版信息

Onco Targets Ther. 2017 Sep 25;10:4719-4729. doi: 10.2147/OTT.S136840. eCollection 2017.

Abstract

Quercetin, a flavone, is multifaceted, having anti-oxidative, anti-inflammatory, and anticancer properties. In the present study, we explored the effects of quercetin on the epithelial-mesenchymal transition (EMT) and invasion of pancreatic cancer cells and the underlying mechanisms. We noted that quercetin exerted pronounced inhibitory effects in PANC-1 and PATU-8988 cells. Moreover, quercetin inhibited EMT and decreased the secretion of matrix metalloproteinase (MMP). Meanwhile, we determined the activity of STAT3 after quercetin treatment. STAT3 phosphorylation decreased following treatment with quercetin. We also used activating agent of STAT3, IL-6, to induce an increase in cell malignancy and to observe the effects of treatment with quercetin. As expected, the EMT and MMP secretion increased with activation of the STAT3 signaling pathway, and quercetin reversed IL-6-induced EMT, invasion, and migration. Therefore, our results demonstrate that quercetin triggers inhibition of EMT, invasion, and metastasis by blocking the STAT3 signaling pathway, and thus, quercetin merits further investigation.

摘要

槲皮素是一种黄酮类化合物,具有多方面的特性,包括抗氧化、抗炎和抗癌特性。在本研究中,我们探究了槲皮素对胰腺癌细胞上皮-间质转化(EMT)和侵袭的影响及其潜在机制。我们发现槲皮素对PANC-1和PATU-8988细胞具有显著的抑制作用。此外,槲皮素抑制EMT并减少基质金属蛋白酶(MMP)的分泌。同时,我们测定了槲皮素处理后STAT3的活性。槲皮素处理后STAT3磷酸化水平降低。我们还使用STAT3激活剂IL-6诱导细胞恶性程度增加,并观察槲皮素处理的效果。正如预期的那样,随着STAT3信号通路的激活,EMT和MMP分泌增加,而槲皮素逆转了IL-6诱导的EMT、侵袭和迁移。因此,我们的结果表明,槲皮素通过阻断STAT3信号通路触发对EMT、侵袭和转移的抑制作用,因此,槲皮素值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9607/5626388/45d3e9da52be/ott-10-4719Fig1.jpg

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