积雪草苷通过 Wnt/β-Catenin 通路破坏 EMT 抑制非小细胞肺癌的生长和转移

IF 4.4 3区 医学 Q2 ENVIRONMENTAL SCIENCES Environmental Toxicology Pub Date : 2024-06-18 DOI:10.1002/tox.24359
Yanan Zhang, Jiangyong Liu, Gang Yang, Jiani Zou, Yan Tan, Erping Xi, Qing Geng, Zheng Wang
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引用次数: 0

摘要

非小细胞肺癌(NSCLC)是全球癌症相关死亡的主要诱因。积雪草苷(ATS)是一种三萜类皂甙,已被证实在多种恶性肿瘤中具有抗肿瘤活性。然而,它在 NSCLC 中的具体功能仍未明确。在这项研究中,NSCLC 细胞暴露于不同剂量的 ATS。通过功能实验来评估 ATS 对 NSCLC 细胞行为的影响。蛋白质表达评估采用了 Western 印迹法。建立了异种移植小鼠模型,以评估 ATS 在体内对 NSCLC 的影响。结果显示,ATS抑制了NSCLC细胞的增殖、细胞周期进展、迁移和侵袭性。ATS 逆转了 TGF-β 诱导的上皮-间质转化(EMT)。从机理上讲,ATS 可抑制 NSCLC 中的 Wnt/β-catenin 信号转导。上调β-catenin可恢复ATS介导的对NSCLC细胞侵袭性的抑制。此外,服用 ATS 还能抑制肿瘤小鼠的肿瘤发生。总之,ATS通过抑制Wnt/β-catenin信号传导阻断EMT,从而抑制NSCLC的生长和转移。
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Asiaticoside Inhibits Growth and Metastasis in Non-Small Cell Lung Cancer by Disrupting EMT via Wnt/β-Catenin Pathway

Non-small cell lung cancer (NSCLC) is the primary inducer of cancer-related death worldwide. Asiaticoside (ATS) is a triterpenoid saponin that has been indicated to possess an antitumor activity in several malignancies. Nonetheless, its detailed functions in NSCLC remain unclarified. In this study, NSCLC cells were exposed to various doses of ATS. Functional experiments were employed to estimate the ATS effect on NSCLC cell behaviors. Western blotting was implemented for protein expression evaluation. A xenograft mouse model was established to assess the ATS effect on NSCLC in vivo. The results showed that ATS restrained NSCLC cell proliferation, cell cycle progression, migration, and invasiveness. ATS reversed TGF-β-induced promotion in epithelial-mesenchymal transition (EMT). Mechanistically, ATS inhibited Wnt/β-catenin signaling in NSCLC. Upregulating β-catenin restored ATS-mediated suppression of NSCLC cell aggressiveness. Moreover, ATS administration repressed tumorigenesis in tumor-bearing mice. In conclusion, ATS represses growth and metastasis in NSCLC by blocking EMT via the inhibition of Wnt/β-catenin signaling.

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来源期刊
Environmental Toxicology
Environmental Toxicology 环境科学-毒理学
CiteScore
7.10
自引率
8.90%
发文量
261
审稿时长
4.5 months
期刊介绍: The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.
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