PDF(Pubmed)
Abstract：
Nasopharyngeal carcinoma (NPC) is prevalent in Asia and exhibits highly metastatic characteristics, leading to uncontrolled disease progression. Isoliquiritigenin (ISL) have attracted attention due to their diverse biological and pharmacological properties, including anticancer activities. However, the impact of ISL on the invasive and migratory ability of NPC remains poorly understood. Hence, this study aimed to investigate the in vitro anti-metastatic effects of ISL on NPC cells and elucidate the underlying signalling pathways. Human NPC cell NPC-39 and NPC-BM were utilized as cell models. Migratory and invasive capabilities were evaluated through wound healing and invasion assays, respectively. Gelatin zymography was employed to demonstrate matrix metalloproteinase-2 (MMP-2) activity, while western blotting was conducted to analyse protein expression levels and explore signalling cascades. Overexpression of signal transducer and activator of transcription 3 (STAT3) was carried out by transduction of STAT3-expressing vector. Our findings revealed that ISL effectively suppressed the migration and invasion of NPC cells. Gelatin zymography and Western blotting assays demonstrated that ISL treatment led to a reduction in MMP-2 enzyme activity and protein expression. Investigation of signalling cascades revealed that ISL treatment resulted in the inhibition of STAT3 phosphorylation. Moreover, overexpression of STAT3 restored the migratory ability of NPC cells in the presence of ISL. Collectively, these findings indicate that ISL inhibits the migration and invasion of NPC cells associating with MMP-2 downregulation through suppressing STAT3 activation. This suggests that ISL has an anti-metastatic effect on NPC cells and has potential therapeutic benefit for NPC treatment.
摘要：
鼻咽癌（NPC）在亚洲普遍存在，并表现出高度转移的特征，导致不受控制的疾病进展。异甘草素（ISL）由于其多样化的生物学和药理学特性而引起了人们的关注，包括抗癌活动。然而,ISL对NPC侵袭和迁移能力的影响尚不清楚。因此，本研究旨在研究ISL对NPC细胞的体外抗转移作用，并阐明其潜在的信号通路。人NPC细胞NPC-39和NPC-BM被用作细胞模型。通过伤口愈合和侵袭分析评估迁移和侵袭能力，分别。明胶酶谱用于证明基质金属蛋白酶-2（MMP-2）活性，同时进行蛋白质印迹分析蛋白质表达水平并探索信号级联。信号转导和转录激活因子3（STAT3）的过表达是通过转导STAT3表达载体进行的。我们的发现表明，ISL有效地抑制了NPC细胞的迁移和侵袭。明胶酶谱和Western印迹分析证明ISL处理导致MMP-2酶活性和蛋白质表达的降低。信号级联的研究揭示ISL处理导致STAT3磷酸化的抑制。此外，在ISL存在下，STAT3的过表达恢复了NPC细胞的迁移能力。总的来说，这些发现表明ISL通过抑制STAT3的激活抑制与MMP-2下调相关的NPC细胞的迁移和侵袭。这表明ISL对NPC细胞具有抗转移作用,并且对于NPC治疗具有潜在的治疗益处。
