Wu Yue, Rong Li, Zhang Suifeng, He Yuxi, Song Na, Zuo Guoqing, Mei Zhechuan
Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Gastroenterology, Bishan Hospital of Chongqing Medical University, Chongqing, China.
Recent Pat Anticancer Drug Discov. 2025;20(2):200-212. doi: 10.2174/0115748928332384240812060751.
(Oliv.) Diels, a renowned traditional Chinese medicine, has gained widespread recognition for its antitumor properties. Further investigation is warranted to determine whether ligustilide (LIG), which is extracted from this plant, can effectively inhibit tumors.
We delved into the impact of LIG on cholangiocarcinoma cells, aiming to unravel the mechanisms underlying its effects.
Cholangiocarcinoma cells (HuccT1 and RBE) were exposed to varying concentrations of LIG (2, 5, 10, 15, 20 μg/mL) for 24, 48, and 72 h. After identifying differentially expressed genes, stable transcription strains were utilized to explore LIG's antitumor mechanism. The inhibitory effects of LIG (5 μg/mL, 48 h) were assessed by CCK-8, colony formation, wound healing, transwell migration, western blotting, and immunofluorescence. , experiments in NOG mice (Ac, Ac+LIG; five per group) evaluated LIG's antiproliferative efficacy (5 mg/kg, intraperitoneal injection, 18-day period).
LIG significantly inhibited cell proliferation and migration with IC 5.08 and 5.77 μg/mL in HuccT1 and RBE cell lines at 48h, increased the expression of E-cadherin while decreased N-cadherin and the protein of PI3K/AKT pathway. Silenced NDRG1 (N-Myc downstream- regulated gene 1) attenuated these effects. , the AC+LIG group (LIG, 5 mg/kg, qd, 18 d) exhibited smaller tumor volumes compared to the Ac group. The expression of Ki-67 was significantly downregulated in the AC+LIG group.
For the first time, our study has revealed that LIG holds therapeutic potential for treating cholangiocarcinoma. These findings hold promise for advancing innovative therapeutic approaches in the treatment of cholangiocarcinoma. LIG may serve as a useful patent for treating CCA.
（羌活）地尔是一种著名的传统中药，其抗肿瘤特性已得到广泛认可。有必要进一步研究从该植物中提取的藁本内酯（LIG）是否能有效抑制肿瘤。
我们深入研究了LIG对胆管癌细胞的影响，旨在揭示其作用的潜在机制。
将胆管癌细胞（HuccT1和RBE）暴露于不同浓度的LIG（2、5、10、15、20μg/mL）中24、48和72小时。在鉴定出差异表达基因后，利用稳定转录菌株探索LIG的抗肿瘤机制。通过CCK-8、集落形成、伤口愈合、Transwell迁移、蛋白质印迹和免疫荧光评估LIG（5μg/mL，48小时）的抑制作用。在NOG小鼠（Ac，Ac+LIG；每组五只）中进行实验，评估LIG的抗增殖功效（5mg/kg，腹腔注射，为期18天）。
LIG在48小时时显著抑制HuccT1和RBE细胞系的细胞增殖和迁移，IC50分别为5.08和5.77μg/mL，增加E-钙黏蛋白的表达，同时降低N-钙黏蛋白和PI3K/AKT通路的蛋白表达。沉默NDRG1（N-Myc下游调控基因1）减弱了这些作用。此外，AC+LIG组（LIG，5mg/kg，qd，18天）的肿瘤体积比Ac组小。AC+LIG组中Ki-67的表达显著下调。
我们的研究首次揭示LIG对治疗胆管癌具有治疗潜力。这些发现为推进胆管癌治疗的创新治疗方法带来了希望。LIG可能是治疗CCA的一种有用药物。
