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二烯丙基三硫抑制胶质瘤细胞的增殖、侵袭和血管生成,作用机制为阻断 Wnt/β-连环蛋白信号通路。

Diallyl trisulfide inhibits proliferation, invasion and angiogenesis of glioma cells by inactivating Wnt/β-catenin signaling.

机构信息

Department of Neurosurgery, Weifang Medical University, Wei-fang City, Shandong Province, China.

Affiliated Bayi Brain Hospital, the PLA Army General Hospital, Beijing, China.

出版信息

Cell Tissue Res. 2017 Dec;370(3):379-390. doi: 10.1007/s00441-017-2678-9. Epub 2017 Aug 17.

DOI:10.1007/s00441-017-2678-9
PMID:28815294
Abstract

Aberrant activation of Wnt/β-catenin signaling leads to increased cell proliferation and survival and promotes the development of various human tumors, including glioma, one of the most common primary brain tumors. The treatment efficacy of many anticancer drugs remains limited or unsatisfactory and it is urgently necessary to develop effective and low-toxicity anticancer drugs or strategies, especially for glioma. Here, we report that diallyl trisulfide suppresses survival, migration, invasion and angiogenesis in glioma cells. These effects were associated with inhibition of the Wnt/β-catenin signaling cascade, which was accompanied by decreased expression of LRP6, TRIM29 and Pygo2. A dual-luciferase reporter assay confirmed that DATS treatment decreased TCF/LEF-mediated transcription. Finally, a nude mouse tumorigenicity model was used to examine the biological effect of diallyl trisulfide in vivo. Consistent with the previous results, diallyl trisulfide inhibited proliferation, invasion and angiogenesis in glioma cells by suppressing Wnt/β-catenin signaling.

摘要

异常激活的 Wnt/β-连环蛋白信号通路导致细胞增殖和存活增加,并促进了各种人类肿瘤的发展,包括神经胶质瘤,这是最常见的原发性脑肿瘤之一。许多抗癌药物的治疗效果仍然有限或不尽如人意,因此迫切需要开发有效且低毒性的抗癌药物或策略,特别是针对神经胶质瘤。在这里,我们报告二烯丙基三硫醚可抑制神经胶质瘤细胞的存活、迁移、侵袭和血管生成。这些作用与抑制 Wnt/β-连环蛋白信号级联有关,同时伴有 LRP6、TRIM29 和 Pygo2 的表达下调。双荧光素酶报告基因检测证实 DATS 处理可降低 TCF/LEF 介导的转录。最后,使用裸鼠肿瘤发生模型在体内研究了二烯丙基三硫醚的生物学效应。与之前的结果一致,二烯丙基三硫醚通过抑制 Wnt/β-连环蛋白信号通路抑制神经胶质瘤细胞的增殖、侵袭和血管生成。

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