Gao Jiahui, Song Yujia, Luo Zanxiang, Su Zejie, Fu Chengshi, Gao Anran, Zhao Jingxiu, Liu Lie, Teng Xiangyun, Xu Jianhua
Department of Laboratory Medicine Shunde Hospital of Guangzhou University of Chinese Medicine Foshan China.
Department of Clinical Laboratory Maoming Hospital of Guangzhou University of Chinese Medicine Maoming China.
Food Sci Nutr. 2025 Jun 18;13(6):e70309. doi: 10.1002/fsn3.70309. eCollection 2025 Jun.
Liver cancer (LC) is among the most prevalent malignant tumors in the digestive tract. The high incidence rate, high metastasis and recurrence rate, poor prognosis, and heterogeneity of liver cancer seriously threaten human health. It is very necessary to search for new drugs and new targets against liver cancer. Natural drugs have been proved to have good anti-tumor effects. Fisetin, a dietary flavonoid often found in fruits and vegetables, has multiple pharmacological functions such as anti-inflammation, anti-oxidation, immune regulation, and anti-tumor. Firstly, we found in vitro that fisetin could inhibit the proliferation, migration, and invasion of liver cancer cells. Bioinformatics analysis speculated that its anti-liver cancer mechanism might be related to the formation of neutrophil extracellular traps (NETs). Then, neutrophils were extracted from healthy volunteers, and it was found that fisetin might inhibit the formation of NETs through the AKT/ROS axis. Then, liver cancer cells were cultured in the medium containing NETs. We found that fisetin could weaken the proliferation, migration, and invasion of liver cancer cells induced by NETs. Finally, we found that fisetin could inhibit tumor growth in C57BL/6 mice. Fisetin could inhibit the recruitment of neutrophils and the level of NETs in tumor tissues. In conclusion, we found that fisetin could be used as a new NETs inhibitor and further clarified the anti-liver cancer effect of fisetin.
肝癌（LC）是消化道中最常见的恶性肿瘤之一。肝癌的高发病率、高转移和复发率、预后不良以及异质性严重威胁着人类健康。寻找抗肝癌的新药和新靶点非常必要。天然药物已被证明具有良好的抗肿瘤作用。非瑟酮是一种常见于水果和蔬菜中的膳食黄酮，具有抗炎、抗氧化、免疫调节和抗肿瘤等多种药理功能。首先，我们在体外发现非瑟酮可以抑制肝癌细胞的增殖、迁移和侵袭。生物信息学分析推测其抗肝癌机制可能与中性粒细胞胞外陷阱（NETs）的形成有关。然后，从健康志愿者中提取中性粒细胞，发现非瑟酮可能通过AKT/ROS轴抑制NETs的形成。接着，将肝癌细胞培养在含有NETs的培养基中。我们发现非瑟酮可以减弱NETs诱导的肝癌细胞的增殖、迁移和侵袭。最后，我们发现非瑟酮可以抑制C57BL/6小鼠的肿瘤生长。非瑟酮可以抑制肿瘤组织中中性粒细胞的募集和NETs的水平。总之，我们发现非瑟酮可以作为一种新的NETs抑制剂，并进一步阐明了非瑟酮的抗肝癌作用。
