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目的：探讨异鼠李素（isorhamnetin,ISO）对喉癌细胞生长、迁移的影响及其与PI3K/AKT1/β-catenin信号的关系。方法：以喉癌细胞株（HEP-2、TU212）、人结肠上皮细胞（NCM460）为研究对象，通过MTT法、克隆形成实验、划痕实验、Transwell实验、台盼蓝染色、Hoechst 33258染色、线粒体膜电位检测、活性氧检测等方法，分析ISO对喉癌细胞生长、迁移的影响；网络药理学及分子对接预测ISO作用于喉癌细胞的分子靶点；Western blot检测喉癌细胞中p-PI3K、p-AKT1、β-catenin和cyclin D1蛋白的表达情况。结果：与对照组（ISO 0μmol/L）比较，ISO(10、20、40μmol/L)明显抑制HEP-2、TU212细胞的增殖、克隆形成、迁移与侵袭，并诱导细胞活性氧水平升高、线粒体膜电位降低，细胞凋亡率升高；网络药理学与分子对接提示ISO可能作用于AKT1分子靶点；Western blot结果发现，不同浓度的ISO(10、20、40μmol/L)处理HEP-2、TU212细胞之后，p-PI3K、p-AKT1、β-catenin和cyclin D1的蛋白表达水平明显低于对照组（P<0.05）。结论：ISO能抑制喉癌细胞的生长、迁移，并通过升高活性氧水平、降低线粒体膜电位诱导细胞凋亡，ISO作用的分子机制可能与调节喉癌细胞的PI3K/AKT1/β-catenin信号通路有关。
Abstract：Objective: To investigate the effects of isorhamnetin(ISO) on the growth and migration of laryngeal cancer cells and its relationship with PI3K/AKT1/β-catenin signaling. Methods: Laryngeal cancer cell lines(HEP-2, TU212) and human colon epithelial cells(NCM460) were used as the research objects, the effects of ISO on the growth and migration of laryngeal cancer cells were analyzed by MTT assay, colony formation assay, scratch assay, Transwell assay, trypan blue staining, Hoechst 33258 staining, mitochondrial membrane potential detection, and reactive oxygen species detection; Network pharmacology and molecular docking were used to predict the molecular targets of ISO on laryngeal cancer cells; Western blot was used to detect the expressions of p-PI3K, p-AKT1, β-catenin, and cyclin D1 protein in laryngeal cancer cells. Results: Compared to the control group(ISO 0 μmol/L), ISO(10, 20, 40 μmol/L) significantly inhibited the proliferation, colony formation, migration, and invasion of HEP-2 and TU212 cells, and induced the increase of reactive oxygen species level, the decrease of mitochondrial membrane potential, and the increase of apoptosis rate. The results of network pharmacology and molecular docking suggested that ISO may have effects on AKT1 molecular targets; Western blot results showed that the protein expression levels of p-PI3K, p-AKT1, β-catenin, and cyclin D1 were significantly lower than those in the control group after HEP-2 and TU212 cells were treated with different concentrations of ISO(10、20、40μmol/L)(P<0.05). Conclusions: ISO can inhibit the growth and migration of laryngeal cancer cells, and induce apoptosis by increasing the level of reactive oxygen species and reducing mitochondrial membrane potential, and its molecular mechanism may be related to the regulation of PI3K/AKT1/β-catenin signaling pathway.
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基本信息:
DOI：10.13210/j.cnki.jhmu.20241213.002
中图分类号:R739.65
引用信息:
[1]余南琼,付一笑,冷东泽,等.异鼠李素对喉癌细胞生长、迁移及PI3K/AKT1/β-catenin信号的抑制作用[J].海南医科大学学报,2026,32(05):362-371.DOI:10.13210/j.cnki.jhmu.20241213.002.
基金信息:
湖北省自然科学基金（2016CFB491）; 湖北科技学院医学科研专项基金（2022YKY07,2022YKY08）;湖北科技学院五官医学院专项基金（2020WG09）~~
2024-12-16
2024-12-16
2024-12-16