State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China.
State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Phytomedicine. 2023 Jun;114:154792. doi: 10.1016/j.phymed.2023.154792. Epub 2023 Mar 30.
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 G/G 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.
结直肠癌（CRC）是一种全球性的恶性疾病。过度激活的 Hedgehog 信号在 CRC 的发病机制中起着重要作用。植物化学物质小檗碱对 CRC 具有很强的作用，但分子机制尚不清楚。
我们旨在研究小檗碱抗 CRC 的作用，并基于 Hedgehog 信号级联探索其潜在机制。
在接受小檗碱处理的 CRC HCT116 细胞和 SW480 细胞中，测量细胞增殖、迁移、侵袭、克隆形成、细胞凋亡和细胞周期，并确定 Hedgehog 信号通路活性。在建立 HCT116 异种移植肿瘤小鼠模型后，研究小檗碱对 CRC 癌变、病理表现和恶性表型的疗效，并分析 HCT116 异种移植肿瘤组织中的 Hedgehog 信号轴。此外，还在斑马鱼上进行了小檗碱的毒理学研究。
发现小檗碱抑制 HCT116 细胞和 SW480 细胞的增殖、迁移、侵袭和克隆形成。此外，小檗碱导致 CRC 细胞凋亡并阻断细胞周期在 G1/G0 期，抑制 Hedgehog 信号级联。在裸鼠的 HCT116 异种移植肿瘤中，小檗碱抑制肿瘤生长，减轻病理评分，并通过抑制 Hedgehog 信号促进肿瘤组织中的细胞凋亡和细胞周期停滞。小檗碱对斑马鱼的毒理学研究表明，小檗碱在高剂量和长时间给药时会对斑马鱼的肝脏和心脏造成损伤。
综上所述，小檗碱可能通过抑制 Hedgehog 信号级联来抑制 CRC 的恶性表型。然而，在滥用小檗碱时，应考虑其潜在的不良反应。
