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DADS 通过下调 LIMK1-ADF/cofilin 抑制结肠癌的迁移和侵袭。

Downregulation of LIMK1-ADF/cofilin by DADS inhibits the migration and invasion of colon cancer.

机构信息

Department of Pathology, The Second Affiliated Hospital, University of South China, Hengyang, Hunan, China.

Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Cancer Research Institute, University of South China, Hengyang, Hunan, China.

出版信息

Sci Rep. 2017 Mar 30;7:45624. doi: 10.1038/srep45624.

Abstract

This study aimed to explore whether the downregulation of LIM kinase 1 (LIMK1)-actin depolymerization factor (ADF, also known as destrin)/cofilin by diallyl disulfide (DADS) inhibited the migration and invasion of colon cancer. Previous studies have shown that silencing LIMK1 could significantly enhance the inhibitory effect of DADS on colon cancer cell migration and invasion, suggesting that LIMK1 was a target molecule of DADS, which needed further confirmation. This study reported that LIMK1 and destrin were highly expressed in colon cancer and associated with poor prognosis of patients with colon cancer. Also, the expression of LIMK1 was positively correlated with the expression of destrin. The overexpression of LIMK1 significantly promoted colon cancer cell migration and invasion. DADS obviously inhibited migration and invasion by suppressing the phosphorylation of ADF/cofilin via downregulation of LIMK1 in colon cancer cells. Furthermore, DADS-induced suppression of cell proliferation was enhanced and antagonized by the knockdown and overexpression of LIMK1 in vitro and in vivo, respectively. Similar results were observed for DADS-induced changes in the expression of vimentin, CD34, Ki-67, and E-cadherin in xenografted tumors. These results indicated that LIMK1 was a potential target molecule for the inhibitory effect of DADS on colon cancer cell migration and invasion.

摘要

本研究旨在探讨二烯丙基二硫(DADS)下调 LIM 激酶 1(LIMK1)-肌动蛋白解聚因子(ADF,也称为肌联蛋白/原肌球蛋白)/丝切蛋白是否抑制结肠癌的迁移和侵袭。先前的研究表明,沉默 LIMK1 可显著增强 DADS 对结肠癌细胞迁移和侵袭的抑制作用,提示 LIMK1 是 DADS 的靶分子,这需要进一步证实。本研究报道 LIMK1 和肌联蛋白在结肠癌中高表达,并与结肠癌患者的不良预后相关。此外,LIMK1 的表达与肌联蛋白的表达呈正相关。LIMK1 的过表达显著促进结肠癌细胞的迁移和侵袭。DADS 通过下调 LIMK1 抑制 ADF/cofilin 的磷酸化,明显抑制结肠癌细胞的迁移和侵袭。此外,在体外和体内,通过敲低和过表达 LIMK1,分别增强和拮抗 DADS 诱导的细胞增殖抑制。在异种移植瘤中,DADS 诱导的波形蛋白、CD34、Ki-67 和 E-钙黏蛋白表达的变化也观察到了类似的结果。这些结果表明,LIMK1 是 DADS 抑制结肠癌细胞迁移和侵袭的潜在靶分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edfb/5372356/c67dd3350e6c/srep45624-f1.jpg

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