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二烯丙基二硫抑制经典 Wnt 信号通路并逆转 A549 肺癌细胞纤连蛋白诱导的上皮间质转化。

Diallyl disulphide suppresses the cannonical Wnt signaling pathway and reverses the fibronectin-induced epithelial mesenchymal transition of A549 lung cancer cells.

机构信息

Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata 700026, India.

出版信息

Food Funct. 2019 Jan 22;10(1):191-202. doi: 10.1039/c8fo00246k.

DOI:10.1039/c8fo00246k
PMID:30516195
Abstract

Globally, non-small cell lung cancer is a leading cause of cancer-related mortality and about 40% of these cancers are detected in the metastatic stage. Epithelial mesenchymal transition (EMT) plays a critical role during malignant transformation, and the extracellular matrix component, fibronectin (FN), is a known inducer of invasion and metastasis. Diallyl disulphide (DADS), a bioactive component of garlic, exhibits a wide spectrum of biological activities including the inhibition of cancer cell migration and invasion. The present study was aimed at deciphering the effect of DADS on the regulation of FN-induced EMT in A549 lung cancer cells. DADS suppressed the FN-induced invasion and migration potential of A549 cells which may be attributed to the reduced activity of gelatinases. DADS suppressed the FN-aggravated EMT of A549 cells by the upregulation of the epithelial markers, E-cadherin and cytokeratin-18, and the downregulation of the mesenchymal markers, N-cadherin and vimentin, and the transcription factors, snail, slug and twist. DADS was effective in inhibiting the nuclear translocation of β-catenin and the phosphorylation of glycogen synthase kinase-3β and in suppressing the activity of dishevelled homolog 2 and T-cell-factor/lymphoid enhancer factor in FN-induced A549 cells. Cumulatively, this study indicated that DADS might be able to reverse FN-induced EMT in A549 cells via the suppression of Wnt signaling.

摘要

全球范围内,非小细胞肺癌是癌症相关死亡的主要原因,其中约 40%的癌症在转移阶段被发现。上皮间质转化(EMT)在恶性转化过程中起着关键作用,细胞外基质成分纤维连接蛋白(FN)是已知的侵袭和转移诱导物。二烯丙基二硫(DADS)是大蒜中的一种生物活性成分,具有广泛的生物学活性,包括抑制癌细胞迁移和侵袭。本研究旨在破译 DADS 对 FN 诱导的 A549 肺癌细胞 EMT 调节的影响。DADS 抑制了 FN 诱导的 A549 细胞的侵袭和迁移潜能,这可能归因于明胶酶活性的降低。DADS 通过上调上皮标志物 E-钙粘蛋白和角蛋白-18,下调间充质标志物 N-钙粘蛋白和波形蛋白,以及转录因子 snail、slug 和 twist,抑制了 FN 加重的 A549 细胞 EMT。DADS 能有效抑制β-连环蛋白的核转位和糖原合成酶激酶-3β的磷酸化,并抑制 Dsh 同源物 2 和 T 细胞因子/淋巴增强因子在 FN 诱导的 A549 细胞中的活性。综上所述,本研究表明,DADS 可能通过抑制 Wnt 信号通路,逆转 FN 诱导的 A549 细胞 EMT。

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