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齐墩果酸通过抑制信号转导和转录激活因子3(STAT3)和紧密连接蛋白1(Claudin-1)抑制鼻咽癌细胞的活力和迁移。

Asiatic Acid Inhibits Nasopharyngeal Carcinoma Cell Viability and Migration via Suppressing STAT3 and Claudin-1.

作者信息

Pantia Supitchaya, Kangsamaksin Thaned, Janvilisri Tavan, Komyod Waraporn

机构信息

Graduate Program in Molecular Medicine, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.

出版信息

Pharmaceuticals (Basel). 2023 Jun 19;16(6):902. doi: 10.3390/ph16060902.

DOI:10.3390/ph16060902
PMID:37375849
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10301974/
Abstract

Nasopharyngeal carcinoma (NPC) is a prevalent cancer in Southeast Asia, but effective treatment options remain limited, and chemotherapy has a high resistance rate. Asiatic acid (AA), a triterpenoid found in , has shown anticancer activity in various cancers. Therefore, this study aims to investigate the anticancer effects and mechanisms of AA in NPC cell lines. The effects of AA on NPC cytotoxicity, apoptosis, and migration were determined in TW-01 and SUNE5-8F NPC cell lines. Western blot analysis was performed to evaluate the protein expression levels affected by AA. The role of AA in proliferation and migration was investigated in STAT3 and claudin-1 knockdown cells. AA inhibited NPC cell viability and migration and induced cell death by increasing cleaved caspase-3 expression. Moreover, AA inhibited STAT3 phosphorylation and reduced claudin-1 expression in NPC cells. Although knockdown of STAT3 or claudin-1 slightly reduced cell viability, it did not enhance the anti-proliferative effect of AA. However, knockdown of STAT3 or claudin-1 increased the anti-migratory effect of AA in NPC cells. These results suggest that AA can be a promising candidate for drug development against NPC.

摘要

鼻咽癌(NPC)是东南亚地区一种常见的癌症,但有效的治疗选择仍然有限,且化疗的耐药率很高。齐墩果酸(AA)是一种存在于[具体来源未提及]中的三萜类化合物,已在多种癌症中显示出抗癌活性。因此,本研究旨在探讨AA对NPC细胞系的抗癌作用及其机制。在TW-01和SUNE5-8F NPC细胞系中测定了AA对NPC细胞毒性、凋亡和迁移的影响。进行蛋白质印迹分析以评估受AA影响的蛋白质表达水平。在STAT3和claudin-1敲低的细胞中研究了AA在增殖和迁移中的作用。AA通过增加裂解的caspase-3表达来抑制NPC细胞活力和迁移并诱导细胞死亡。此外,AA抑制NPC细胞中STAT3的磷酸化并降低claudin-1的表达。虽然敲低STAT3或claudin-1会略微降低细胞活力,但并未增强AA的抗增殖作用。然而,敲低STAT3或claudin-1会增强AA对NPC细胞的抗迁移作用。这些结果表明,AA有望成为开发抗NPC药物的候选物。

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