Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, 1677 Wutaishan Road, Qingdao, 266003, People's Republic of China.
Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People's Republic of China.
Mol Biol Rep. 2024 Jul 23;51(1):842. doi: 10.1007/s11033-024-09738-5.
Although Huaier granules can be used as prospective anti-cholangiocarcinoma drugs, the mechanism of action of Huaier granules in cholangiocarcinoma is not clear. The anti-cholangiocarcinoma effect of Huaier granules was validated in cell line research. In vitro experiments were conducted to investigate the signalling pathways affected by Huaier in CCA cells.
Real-time quantitative PCR (RT‒qPCR) and Western blot analysis were performed to analyse gene expression in CCA cells. MTT assays, scratch tests, and Transwell assays were used to explore the effects on the proliferation and metastasis of CCA cells. Chromatin immunoprecipitation assays were performed to reveal the potential underlying mechanisms involved. Twist1 was upregulated in human CCA tissues. In addition, its expression levels were negatively related to FBP1 expression levels. Mechanistically, Twist1 can bind to the region of the FBP1 promoter to reduce its expression. Huaier plays an indispensable role in suppressing Twist1 expression to inhibit the Twist1/FBP1/Wnt/β-catenin axis. Then, we verified the effect of Huaier in vitro.
These findings suggested that Huaier granules were capable of inhibiting CCA development through regulating the Twist1/FBP1/Wnt/β-catenin signalling axis and provided a novel orientation for the development of novel anti-CCA drugs.
虽然槐耳颗粒可用作有前途的抗胆管癌药物，但槐耳颗粒在胆管癌中的作用机制尚不清楚。在细胞系研究中验证了槐耳颗粒的抗胆管癌作用。进行了体外实验以研究槐耳在 CCA 细胞中影响的信号通路。
实时定量 PCR（RT-qPCR）和 Western blot 分析用于分析 CCA 细胞中的基因表达。MTT 测定、划痕试验和 Transwell 测定用于探索对 CCA 细胞增殖和转移的影响。进行染色质免疫沉淀测定以揭示涉及的潜在潜在机制。Twist1 在人 CCA 组织中上调。此外，其表达水平与 FBP1 表达水平呈负相关。Twist1 可以与 FBP1 启动子区域结合以降低其表达。槐耳在抑制 Twist1 表达以抑制 Twist1/FBP1/Wnt/β-catenin 轴方面发挥不可或缺的作用。然后，我们在体外验证了槐耳的作用。
这些发现表明，槐耳颗粒能够通过调节 Twist1/FBP1/Wnt/β-catenin 信号通路抑制 CCA 的发展，并为开发新型抗 CCA 药物提供了新的方向。
