研究动态
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藁本内酯抑制 PI3K/AKT 信号通路并抑制胆管癌细胞增殖、迁移和侵袭。

Ligustilide Inhibits the PI3K/AKT Signalling Pathway and Suppresses Cholangiocarcinoma Cell Proliferation, Migration, and Invasion.

发表日期:2024 Aug 20
作者: Yue Wu, Li Rong, Suifeng Zhang, Yuxi He, Na Song, Guoqing Zuo, Zhechuan Mei
来源: Cellular & Molecular Immunology

摘要:

当归是一种著名的中药,因其抗肿瘤特性而受到广泛认可。从这种植物中提取的藁本内酯(LIG)是否能有效抑制肿瘤,还需要进一步研究。我们深入研究了LIG对胆管癌细胞的影响,旨在揭示其作用机制。胆管癌细胞(HuccT1和RBE) )分别暴露于不同浓度的LIG(2、5、10、15、20μg/mL)中24、48和72小时。鉴定出差异表达基因后,利用稳定转录株来探索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(5 μg/mL,48 小时)的抑制作用。在体内,NOG小鼠实验(Ac、Ac LIG;每组5只)评估了LIG的抗增殖功效(5 mg/kg,腹腔注射,18天)。LIG显着抑制细胞增殖和迁移,IC50分别为5.08和5.77 μg/ mL在HuccT1和RBE细胞系中作用48小时,增加了E-cadherin的表达,同时降低了N-cadherin和PI3K/AKT通路蛋白的表达。沉默的 NDRG1(N-Myc 下游调节基因 1)减弱了这些影响。在体内,与 Ac 组相比,AC LIG 组(LIG,5 mg/kg,每日一次,18 天)表现出更小的肿瘤体积。 AC LIG组中Ki-67的表达显着下调。我们的研究首次揭示了LIG具有治疗胆管癌的潜力。这些发现有望推动胆管癌治疗的创新治疗方法。 LIG 可以作为治疗 CCA 的有用专利。版权所有 © Bentham Science Publishers;如有任何疑问,请发送电子邮件至 epub@benthamscience.net。
Angelica sinensis (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. In vivo, 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 IC50 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. In vivo, 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.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.