Mechanistic insights into Aloin-mediated regulation of STAT3/SLC7A11 signaling in head and neck squamous cell carcinoma.

IF 2 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cytotechnology Pub Date : 2025-08-01 Epub Date: 2025-07-03 DOI:10.1007/s10616-025-00798-4

Li-Jian Wang, Jun Wang

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引用次数: 0

Abstract

This study aims to investigate the mechanisms by which Aloin (AloAB) mediates the signal transducer and activator of transcription 3 (STAT3)/solute carrier family 7 member 11 (SLC7A11) signaling pathway in head and neck squamous cell carcinoma (HNSCC). HNSCC cells were treated with 50-1000 μM AloAB to assess dose-dependent cytotoxicity and its effects on the STAT3/SLC7A11 pathway. CRISPR activation plasmids were used to overexpress STAT3 or SLC7A11 in FaDu cells. Subsequent analyses included migration and invasion assays, lipid peroxidation (LPO) assay, intracellular iron assay, as well as the measurement of oxidative stress markers and ferroptosis-related factors. Epithelial-mesenchymal transition (EMT) markers and matrix metalloproteinase (MMP) expression levels were also assessed. AloAB treatment significantly reduced cell viability in HNSCC cells at higher concentrations. It inhibited FaDu cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while downregulating STAT3/SLC7A11 expression. Additionally, AloAB induced oxidative stress and ferroptosis, as indicated by elevated malondialdehyde (MDA), Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4), lipid peroxidation (LPO), and iron levels, alongside decreased levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase 4 (GPX4), reduced glutathione (GSH), and glutathione peroxidase (GPx). Overexpression of STAT3 or SLC7A11 reversed these effects, restoring oxidative stress markers and ferroptosis-related factors to control levels. Moreover, the suppression of EMT was alleviated by the upregulation of E-cadherin and the downregulation of N-cadherin, Vimentin, MMP2, and MMP9. AloAB exerts anti-tumor effects on HNSCC cells by inhibiting the STAT3/SLC7A11 signaling pathway, inducing oxidative stress, ferroptosis, and suppression of migration, invasion, and EMT.

Supplementary information: The online version contains supplementary material available at 10.1007/s10616-025-00798-4.

查看原文本刊更多论文

aloin介导的STAT3/SLC7A11信号在头颈部鳞状细胞癌中的调控机制

本研究旨在探讨芦荟素（AloAB）在头颈部鳞状细胞癌（HNSCC）中介导转录3 (STAT3)/溶质载体家族7成员11 （SLC7A11）信号通路的机制。用50-1000 μM AloAB处理HNSCC细胞，评估剂量依赖性细胞毒性及其对STAT3/SLC7A11通路的影响。利用CRISPR激活质粒在FaDu细胞中过表达STAT3或SLC7A11。随后的分析包括迁移和侵袭试验，脂质过氧化（LPO）试验，细胞内铁含量测定，以及氧化应激标志物和铁中毒相关因素的测定。同时评估上皮-间质转化（EMT）标志物和基质金属蛋白酶（MMP）的表达水平。高浓度AloAB处理显著降低HNSCC细胞活力。抑制FaDu细胞增殖、迁移、侵袭和上皮间质转化（EMT），下调STAT3/SLC7A11表达。此外，AloAB诱导氧化应激和铁下垂，表现为丙二醛（MDA）、酰基辅酶a合成酶长链家族成员4 （ACSL4）、脂质过氧化（LPO）和铁水平升高，同时超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶4 （GPX4）、还原性谷胱甘肽（GSH）和谷胱甘肽过氧化物酶（GPx）水平降低。STAT3或SLC7A11的过表达逆转了这些作用，将氧化应激标志物和铁中毒相关因子恢复到控制水平。此外，E-cadherin的上调和N-cadherin、Vimentin、MMP2、MMP9的下调减轻了EMT的抑制。AloAB通过抑制STAT3/SLC7A11信号通路，诱导氧化应激、铁下垂，抑制迁移、侵袭和EMT，对HNSCC细胞发挥抗肿瘤作用。补充信息：在线版本包含补充资料，可在10.1007/s10616-025-00798-4获得。

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来源期刊

Cytotechnology 生物-生物工程与应用微生物

CiteScore

4.10

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The scope of the Journal includes: 1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products. 2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools. 3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research. 4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy. 5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.