Li Jike, Wang Yuelian, Bao Lei, Chen Guo, Ye Qing, He Chengshi, Liu Lin, Luo Mei
Traditional Chinese Medicine Laboratory, Chengdu Public Health Clinical Center, Chengdu, 610061, People's Republic of China.
Center for Precision and Translational Medicine, Chengdu Public Health Clinical Center, Chengdu, 610061, People's Republic of China.
Hum Cell. 2025 Jan 3;38(2):37. doi: 10.1007/s13577-024-01168-6.
Hepatocellular carcinoma (HCC) is a primary malignant neoplasm exhibiting a high mortality rate. Taxifolin is a naturally occurring flavonoid compound that exhibits a range of pharmacological properties. The effects of taxifolin on HCC remain largely unexplored. Therefore, the aim of this study was to examine the potential roles of taxifolin in the development and progression of HCC. In this study, CCK-8 assay was utilized to examine the impact of taxifolin on the cell viability. The copper ions level and the activity of mitochondrial respiratory chain were determined by the correspondent kits. The biological properties of HCC cells were evaluated using colony formation, transwell, flow cytometry, and TUNEL assays, respectively. Transcriptome sequencing was carried out either with or without taxifolin treatment. The expression of cuproptosis-related proteins was determined by Western blot. We observed significant decrease of cell viability, Glutathione (GSH), and mitochondrial respiratory chain under the treatment of taxifolin, while an increase of copper ions level. Taxifolin was observed to suppress HCC progression both in vitro and in vivo. The intersection analysis was performed between upregulated genes and cuproptosis-related genes to obtain one intersection gene-SLC31A1. The knockdown of SLC31A1 reversed the tumor-suppressive effects induced by taxifolin. Taxifolin inhibited HCC progression through inducing cuproptosis in an SLC31A1-mediated manner.
肝细胞癌（HCC）是一种死亡率很高的原发性恶性肿瘤。紫杉叶素是一种天然存在的黄酮类化合物，具有一系列药理特性。紫杉叶素对HCC的影响在很大程度上仍未得到探索。因此，本研究的目的是探讨紫杉叶素在HCC发生发展中的潜在作用。在本研究中，采用CCK-8法检测紫杉叶素对细胞活力的影响。用相应试剂盒测定铜离子水平和线粒体呼吸链活性。分别采用集落形成、Transwell、流式细胞术和TUNEL法评估肝癌细胞的生物学特性。在有或没有紫杉叶素处理的情况下进行转录组测序。通过蛋白质免疫印迹法测定铜死亡相关蛋白的表达。我们观察到在紫杉叶素处理下细胞活力、谷胱甘肽（GSH）和线粒体呼吸链显著降低，而铜离子水平升高。观察到紫杉叶素在体外和体内均能抑制HCC进展。对上调基因和铜死亡相关基因进行交集分析，得到一个交集基因——SLC31A1。敲低SLC31A1可逆转紫杉叶素诱导的肿瘤抑制作用。紫杉叶素通过以SLC31A1介导的方式诱导铜死亡来抑制HCC进展。
