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二烯丙基二硫醚拮抗 DJ-1 介导的胃癌细胞增殖、上皮-间充质转化和化疗耐药性。

Diallyl disulfide antagonizes DJ-1 mediated proliferation, epithelial-mesenchymal transition, and chemoresistance in gastric cancer cells.

机构信息

Hunan Clinical Research Center for Gastric Cancer Prevention and Treatment, Second Affiliated hospital, University of South China, Hengyang, China.

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

出版信息

Environ Toxicol. 2024 Aug;39(8):4105-4119. doi: 10.1002/tox.24300. Epub 2024 Apr 20.

DOI:10.1002/tox.24300
PMID:38642008
Abstract

Diallyl disulfide (DADS), an organic component of allicin abstracted from garlic, possesses multi-target antitumor activity. DJ-1 performs a vital function in promoting AKT aberrant activation via down-regulating phosphatase and tensin homologue (PTEN) in tumors. It is unknown the involvement of DJ-1 in epithelial-mesenchymal transition (EMT) of gastric cancer (GC) cells. The purpose of this study is to investigate whether diallyl disulfide (DADS) intervenes in the role of DJ-1 in GC. Based on the identification that the correlation between high DJ-1 and low PTEN expression in GC was implicated in clinical progression, we illuminated that down-regulation of DJ-1 by DADS aided in an increase in PTEN expression and a decrease in phosphorylated AKT levels, which was in line with the results manifested in the DJ-1 knockdown and overexpressed cells, concurrently inhibiting proliferation, EMT, migration, and invasion. Furthermore, the antagonistic effects of DADS on DJ-1 were observed in in vivo experiments. Additionally, DADS mitigated the DJ-1-associated drug resistance. The current study revealed that DJ-1 is one of potential targets for DADS, which hopefully provides a promising strategy for prevention and adjuvant chemotherapy of GC.

摘要

二烯丙基二硫(DADS)是从大蒜中提取的大蒜素的有机成分,具有多种靶向抗肿瘤活性。DJ-1 在肿瘤中通过下调磷酸酶和张力蛋白同源物(PTEN)来发挥促进 AKT 异常激活的重要功能。DJ-1 是否参与胃癌(GC)细胞的上皮-间充质转化(EMT)尚不清楚。本研究旨在探讨二烯丙基二硫(DADS)是否干预 DJ-1 在 GC 中的作用。基于 DJ-1 高表达与 GC 中低 PTEN 表达之间的相关性与临床进展有关的鉴定,我们发现 DADS 通过下调 DJ-1 有助于增加 PTEN 表达和降低磷酸化 AKT 水平,这与 DJ-1 敲低和过表达细胞中的结果一致,同时抑制增殖、EMT、迁移和侵袭。此外,在体内实验中观察到 DADS 对 DJ-1 的拮抗作用。此外,DADS 减轻了 DJ-1 相关的耐药性。本研究表明 DJ-1 是 DADS 的潜在靶点之一,有望为 GC 的预防和辅助化疗提供有前景的策略。

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