Diallyl disulfide effect on the invasion and migration ability of HL-60 cells with a high expression of DJ-1 in the nucleus through the suppression of the Src signaling pathway.

Diallyl disulfide effect on the invasion and migration ability of HL-60 cells with a high expression of DJ-1 in the nucleus through the suppression of the Src signaling pathway.
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DOI:
10.3892/ol.2018.8139
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发表时间:
2018-05
期刊:
影响因子:
2.9
通讯作者:
Tan H
Tan H
中科院分区:
医学4区
文献类型:
--
作者:
Liu R;Yang YN;Yi L;Qing J;Li QY;Wang WS;Wang J;Tang YX;Tan H

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本研究探讨了二烯丙基二硫(DADS)对帕金森病相关脱糖酶(DJ-1)核内高表达HL-60细胞(HHDN)侵袭和迁移能力的影响及其分子机制。蛋白质印迹分析用于测量DADS和Src抑制剂对HHDN中DJ-1的表达和Src信号通路的影响。采用Transwell迁移实验和侵袭小室实验检测DADS和Src抑制剂对HHDN侵袭和迁移能力的影响。实验分为对照组(HL-60细胞)、空载体组和高表达组(HHDN细胞)。Western blot结果显示,DADS处理24、48和72 h后,DJ-1的表达呈时间依赖性受到抑制。DADS处理后,与未处理组相比,各组磷酸化Src(p-Src)和磷酸化Fak(p-Fak)的表达均明显下降,而Src、Fak和整合素的表达水平无明显变化。Western blot分析结果显示,与未处理组相比,DADS和Src抑制剂处理后,3组p-Src和p-Fak的表达水平均显著降低,而Src、Fak和整合素的表达水平无显著变化。DADS和Src抑制剂处理HHND 24、48和72 h后,DJ-1的表达呈时间依赖性抑制。Transwell迁移和侵袭试验结果显示,DADS和Src抑制剂可以抑制白血病细胞的迁移和侵袭,并且两种治疗的组合可能导致更有效的抑制。DADS可能通过抑制Src-Fak-Integrin信号通路下调DJ-1介导的白血病细胞侵袭和迁移,Src抑制剂可能增强DADS的抗肿瘤作用。
The present study examined the effect of diallyl disulfide (DADS) on the invasion and migration ability of HL-60 cells with a high expression of parkinsonism associated deglycase (DJ-1) in the nucleus (HHDN), and its molecular mechanism. A western blot assay was used to measure the effects of DADS and an Src inhibitor on the expression of DJ-1 and the Src signal pathway in HHDN. The effects of DADS and Src inhibitors on the invasion and migration ability of HHDN was detected using Transwell migration and invasion chamber experiments. The experiments were divided into three groups: A control group (HL-60 cells), an empty vector group and a high expression group (HHDN cells). Western blot assays revealed that the expression of DJ-1 in HHDN was inhibited in a time-dependent manner following treatment with DADS for 24, 48 and 72 h. Following DADS treatment, the expression of phosphorylated Src (p-Src) and phosphorylated Fak (p-Fak) were significantly decreased in all groups compared with the untreated groups, however the expression level of Src, Fak and integrin did not change significantly. Western blot analysis results revealed that following treatment with DADS and Src inhibitor, the expression levels of p-Src and p-Fak significantly decreased in all three groups compared with untreated groups, whereas the expression levels of Src, Fak and integrin did not change significantly. The expression of DJ-1 in HHND was inhibited in time-dependent manner following treatment with DADS and Src inhibitor for 24, 48 and 72 h. Transwell migration and invasion assay results revealed that DADS and Src inhibitors may suppress migration and invasion in leukemic cells, and a combination of the two treatments may result in more efficient suppression. DADS may downregulate DJ-1-mediated invasion and migration in leukemic cells through suppressing the Src-Fak-Integrin signaling pathway, and the Src inhibitor may enhance the antitumor effect of DADS.
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