Hu Xuekai, Zhang Yue, Li Yanchen, Zheng Qiuxia, Zhao Haixia, Zhang Yun, Ni Jingman, Yao Jia
School of Pharmacy, Lanzhou University, Lanzhou, 730000, People's Republic of China.
The First school of Clinical Medicine, Lanzhou University, Lanzhou, 730000, People's Republic of China.
Sci Rep. 2025 Jul 2;15(1):22870. doi: 10.1038/s41598-025-06127-1.
The clinical manifestations of intrahepatic cholangiocarcinoma (ICC) are non-specific, and few patients qualify for surgical resection at diagnosis, thus limiting treatment options. Anticancer peptides (ACPs) exhibit potent tumour inhibition, minimal side effects, easy modification, and low production costs, making them promising for clinical use. Simultaneously, the development of patient-derived three-dimensional organoids as a novel disease model has enabled the replication of the structure and heterogeneity of solid tumours. These organoids provide valuable tools for understanding disease mechanisms, conducting drug sensitivity tests, and developing targeted therapies. However, ACPs' effect on ICC organoids remain unclear. Therefore, this study aims to explore the potential of ACPs in treating ICC using patient-derived organoids (PDOs). We designed and synthesised a series of ACPs sequences and applied them to PDOs model. The organoid model exhibits histological and genomic characteristics similar to those of maternal tumours. Drug sensitivity revealed that ACPs affected the growth of tumour cells and exerted anticancer effects through direct membrane disruption and indirect induction of apoptosis. In this study, organoids can be used as an in vitro model to evaluate the therapeutic response of ACPs and offer novel insight for the study of ICC.
肝内胆管癌（ICC）的临床表现不具有特异性，诊断时很少有患者符合手术切除条件，从而限制了治疗选择。抗癌肽（ACP）具有强大的肿瘤抑制作用、副作用极小、易于修饰且生产成本低，使其具有临床应用潜力。同时，患者来源的三维类器官作为一种新型疾病模型的发展，能够复制实体瘤的结构和异质性。这些类器官为理解疾病机制、进行药物敏感性测试以及开发靶向治疗提供了有价值的工具。然而，ACP对ICC类器官的影响仍不清楚。因此，本研究旨在利用患者来源的类器官（PDO）探索ACP治疗ICC的潜力。我们设计并合成了一系列ACP序列，并将其应用于PDO模型。类器官模型表现出与母肿瘤相似的组织学和基因组特征。药物敏感性显示，ACP通过直接破坏细胞膜和间接诱导凋亡影响肿瘤细胞生长并发挥抗癌作用。在本研究中，类器官可作为体外模型来评估ACP的治疗反应，并为ICC研究提供新的见解。
