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文章:

二硫化物(DADS)在HER2阳性乳腺癌细胞中对侵袭潜能及β-连环蛋白动态的双重作用

Dual Role of Diallyl Disulfide (DADS) on Invasive Potential and β-Catenin Dynamics in HER2-Positive Breast Cancer Cells

原文发布日期:5 November 2025

DOI: 10.3390/cancers17213572

类型: Article

开放获取: 是

 

英文摘要:

Background/Objectives:Natural compounds are being increasingly explored as potential adjuvants to conventional drugs in oncological treatments. Regarding breast tumors, several studies indicate that garlic (Allium sativum) may protect against onset, counteracts aggressiveness, and prevents malignant progression of cells from non-invasive tumors. It has been widely demonstrated that garlic derivatives induce apoptosis and reduce invasive potential in ER-positive and triple-negative breast tumor cells. However, the current literature lacks studies investigating their effects on HER2-positive (HER2+) breast cancers. This study therefore aimed to explore the effects of a garlic extract and diallyl disulfide (DADS), one of its most bioactive organosulfur compounds, on HER2+ phenotype breast tumor cells.Methods:The effects of a garlic extract and diallyl disulfide (DADS) were investigated on MDA-MB-453 and SKBR3 breast tumor cell lines. Cell growth, invasive potential, and Akt-related signaling were assessed after 4–72 h of garlic derivatives administration. The intracellular localization of β-catenin was examined with immunofluorescent confocal microscopy.Results:A dual role of DADS, dependent on the duration of treatment, was revealed. Acute administration induced a significant decrease in invasive potential, while prolonged treatment promoted HER2+ cell invasiveness. These effects were directly correlated with the activation of Akt and the nuclear accumulation of β-catenin, known to induce expression of genes associated with tumor malignancy.Conclusions:Although further investigations are needed to establish the exact mechanism and to assess the in vivo reproducibility of these phenomena, our results highlight the heterogeneous response to natural compounds of complex diseases like cancer.

 

摘要翻译: 

背景/目的:天然化合物作为肿瘤治疗中常规药物的潜在辅助剂正日益受到关注。针对乳腺肿瘤,多项研究表明大蒜可能具有预防肿瘤发生、抑制侵袭性及阻止非浸润性肿瘤细胞恶性进展的作用。已有充分证据表明,大蒜衍生物能诱导ER阳性及三阴性乳腺肿瘤细胞凋亡并降低其侵袭潜能。然而,现有文献尚缺乏关于其对HER2阳性乳腺癌作用的研究。因此,本研究旨在探讨大蒜提取物及其最具生物活性的有机硫化合物之一——二烯丙基二硫醚对HER2阳性表型乳腺肿瘤细胞的影响。 方法:研究采用MDA-MB-453和SKBR3乳腺肿瘤细胞系,评估大蒜提取物及二烯丙基二硫醚的作用效果。在给予大蒜衍生物处理4-72小时后,检测细胞生长、侵袭潜能及Akt相关信号通路变化。通过免疫荧光共聚焦显微镜观察β-连环蛋白的细胞内定位。 结果:研究发现二烯丙基二硫醚具有双重作用,其效应取决于处理时长。急性给药可显著降低细胞侵袭潜能,而长期处理反而促进HER2阳性细胞的侵袭性。这些效应与Akt的激活及β-连环蛋白的核内积聚直接相关,已知这两种机制可诱导肿瘤恶性相关基因的表达。 结论:尽管需要进一步研究以明确其确切机制并评估这些现象在体内的可重复性,但我们的研究结果凸显了癌症这类复杂疾病对天然化合物的异质性反应。

 

 

原文链接:

Dual Role of Diallyl Disulfide (DADS) on Invasive Potential and β-Catenin Dynamics in HER2-Positive Breast Cancer Cells

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