大肠癌（CRC）是全球人类所面临严重疾病之一。高度活化的“刺猬”信号在CRC的发病中扮演着极为重要的角色。植物化学物质黄连碱对CRC具有很强的抑制作用，其分子机制尚不清楚。我们旨在研究黄连碱抗CRC的作用并在“刺猬”信号瀑布级联中探讨其潜在机理。我们测试了经过黄连碱处理的CRC HCT116和SW480细胞的增殖、迁移、浸润、克隆形成、细胞凋亡和细胞周期，并测量了“刺猬”信号通路的活性。在建立的HCT116异种移植瘤小鼠模型中，评估了黄连碱对CRC的发生、病理表现和恶性表型的功效，分析了HCT116异种移植瘤组织中的“刺猬”信号轴。此外，我们还对斑马鱼进行了黄连碱的毒理学研究。研究结果表明，黄连碱可抑制HCT116和SW480细胞的增殖、迁移、浸润和克隆形成等功能。此外，它还引起了细胞凋亡，阻滞了CRC细胞在G0/G1时期的细胞周期，并减弱“刺猬”信号的级联反应。在裸鼠的HCT116异种移植瘤中，黄连碱抑制了肿瘤的生长，缓解了病理评分，并促进了肿瘤组织的细胞凋亡和细胞周期阻滞，通过压制“刺猬”信号的级联反应实现。黄连碱在斑马鱼上的毒理学研究表明，高剂量和长期使用黄连碱可能会损害鱼肝和心脏。总之，黄连碱可以通过降低“刺猬”信号的级联反应来抑制CRC的恶性表型。但需要注意的是，滥用黄连碱可能会带来潜在的不良反应。© 2023 Elsevier GmbH保留所有权利。

Colorectal cancer (CRC) is a malignant affliction that burdens people globally. Overactivated Hedgehog signal is highly implicated in CRC pathogenesis. Phytochemical berberine exerts strong potency on CRC, with molecular mechanism elusive.We sought to study berberine's anti-CRC action and explore its underlying mechanism based on Hedgehog signaling cascade.In CRC HCT116 cells and SW480 cells treated with berberine, the proliferation, migration, invasion, clonogenesis, apoptosis and cell cycle were measured, with determination of Hedgehog signaling pathway activity. Following establishment of mouse model of HCT116 xenograft tumor, the efficacies of berberine on carcinogenesis, pathological manifestation and malignant phenotypes of CRC were examined, with analysis of Hedgehog signaling axis in HCT116 xenograft tumor tissues. Additionally, toxicological study of berberine was conducted on zebrafish.Berberine was discovered to suppress the proliferation, migration, invasion and clonogenesis of HCT116 cells and SW480 cells. Furthermore, berberine caused cell apoptosis and blockaded cell cycle at phase G0/G1 in CRC cells, with dampened Hedgehog signaling cascade. In HCT116 xenograft tumor of nude mice, berberine inhibited tumor growth, alleviated pathological score, and promoted apoptosis and cell cycle arrest in tumor tissues, through constraining Hedgehog signaling. The toxicological study of berberine on zebrafish indicated that berberine incurred damage to the liver and heart of zebrafish at high dosage and prolonged administration.Taken together, berberine may inhibit the malignant phenotypes of CRC through diminishing Hedgehog signaling cascade. However, the potential adverse reactions should be taken into account upon abuse of berberine.Copyright © 2023 Elsevier GmbH. All rights reserved.