Dihydroartemisinin targets ANXA2 to suppress hepatocellular carcinoma angiogenesis through the PI3K/AKT signaling pathway

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-08-13 DOI:10.1016/j.tice.2025.103087

Lulu Cao , Lihui Wang , Jun Lin , Jian Zhao , Bolun Xu , Jianxin Chen , Juanjuan Hu , Siwei Wang , Junhua Yu

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引用次数: 0

Abstract

Background

Annexin A2 (ANXA2), implicated in the progression of multiple cancers, is considered a promising biomarker for anti-cancer therapies. Our research explores the molecular mechanisms of ANXA2 in hepatocellular carcinoma (HCC) and discovers the potential of traditional Chinese medicine compounds to target ANXA2, aiming to improve current HCC therapeutic approaches.

Methods

Our study leveraged TCGA data to investigate ANXA2 expression in HCC, complemented by gene set enrichment analysis to elucidate its potential impact. We quantified ANXA2 expressions in HCC cells using qRT-PCR and western blot. Modulating ANXA2 expression, we used cell counting kit-8 to gauge cell viability and Transwell assays to measure invasiveness. Scratch and tube formation assays were conducted on human umbilical vein endothelial cells (HUVECs), and vascular endothelial growth factor A (VEGFA) levels were detected via enzyme-linked immunosorbent assay. Molecular docking with AutoDock and cell thermal shift assays established the binding affinity and targeting of dihydroartemisinin (DHA) to ANXA2.

Results

ANXA2 was upregulated in HCC tissues and cells and was particularly enriched in the PI3K/AKT signaling pathway. Knockdown of ANXA2 in HCC cells resulted in the inhibition of cell invasion and angiogenesis, while overexpression led to the opposite effects. We discovered a binding relationship between DHA and ANXA2, suggesting that the therapeutic effects of DHA on HCC are mediated through targeting ANXA2.

Conclusion

DHA, by engaging ANXA2, mitigates the PI3K/AKT signaling, thereby inhibiting invasive and angiogenic activities of HCC.

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双氢青蒿素通过PI3K/AKT信号通路靶向ANXA2抑制肝癌血管生成

dannexin A2 （ANXA2）与多种癌症的进展有关，被认为是一种有前景的抗癌治疗生物标志物。我们的研究探索了ANXA2在肝细胞癌（HCC）中的分子机制，并发现了靶向ANXA2的中药化合物的潜力，旨在改善目前HCC的治疗方法。方法本研究利用TCGA数据研究ANXA2在HCC中的表达，并辅以基因集富集分析来阐明其潜在影响。我们使用qRT-PCR和western blot方法定量了ANXA2在HCC细胞中的表达。通过调节ANXA2的表达，我们使用细胞计数试剂盒-8来测量细胞活力，并使用Transwell法来测量侵袭性。对人脐静脉内皮细胞（HUVECs）进行划痕和成管实验，并通过酶联免疫吸附法检测血管内皮生长因子A （VEGFA）水平。AutoDock分子对接和细胞热移实验确定了双氢青蒿素（DHA）与ANXA2的结合亲和力和靶向性。结果sanxa2在HCC组织和细胞中表达上调，并在PI3K/AKT信号通路中富集。在HCC细胞中，下调ANXA2可抑制细胞侵袭和血管生成，而过表达则会产生相反的效果。我们发现DHA与ANXA2之间存在结合关系，提示DHA对HCC的治疗作用是通过靶向ANXA2介导的。结论dha通过参与ANXA2，减轻PI3K/AKT信号，从而抑制HCC的侵袭性和血管生成活性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.