Zeng Sha, Wang Juan, Shi Zhengrong, Zhao Hui, Gao Jingxing, Li Jinxiu
Chengdu Integrated TCM and Western Medicine Hospital, Department of Traditional Chinese Medicine Pharmacy, Chengdu, China.
Henan University of Traditional Chinese Medicine, Department of pharmacology, Zhengzhou, Henan, China.
Front Pharmacol. 2025 Apr 10;16:1560714. doi: 10.3389/fphar.2025.1560714. eCollection 2025.
Colorectal cancer (CRC) is globally recognized as the third most frequently diagnosed malignancy and the second leading cause of cancer-related mortality. The etiology of CRC is multifactorial, arising from a complex interplay of genetic alterations, environmental exposures, and age-related physiological changes. Among the numerous signaling pathways that regulate cellular homeostasis, the Wnt/β-catenin signaling pathway not only plays a critical role in embryonic development and cell proliferation but also contributes to the initiation and progression of various malignancies, including CRC. Dysregulation of the Wnt/β-catenin signaling pathway is a hallmark of CRC, playing a pivotal role in regulating chemoresistance and driving invasive and metastatic behaviors. Traditional Chinese Medicine (TCM) is characterized by its multi-target and multi-pathway mechanisms. Extensive studies have demonstrated that TCM can inhibit the activity of CRC cells by targeting the Wnt/β-catenin signaling pathway and significantly alleviate symptoms in CRC animal models, demonstrating its potential therapeutic value for the treatment of CRC. This review primarily focuses on the literature published in the past 5 years, retrieved from databases such as PubMed, Web of Science, Scopus, MEDLINE, and Springer, concerning the targeting of the Wnt/β-catenin signaling pathway for the treatment of CRC. It highlights the research progress on TCM monomers (e.g., myricetin, genistein, baicalein), TCM formulations (e.g., Pai-Nong-San (PNS), Jian-Du-Xiao-Sheng Yin (JXY), Zuo-Jin-Wan (ZJW)), and small-molecule inhibitors (e.g., PCDHGA9, Cetuximab, PTK7). Furthermore, the experimental results and conclusions from these studies are thoroughly analyzed and discussed. Through a comprehensive review of the literature, we conclude that TCM exhibits multi-level, multi-target, and multi-faceted effects in the prevention and treatment of CRC. In-depth research into the mechanisms by which TCM targets the Wnt/β-catenin signaling pathway to prevent and treat CRC may provide novel insights into exploring the pathogenesis of CRC and developing new therapeutic agents for CRC.
结直肠癌（CRC）在全球范围内被公认为是第三大最常被诊断出的恶性肿瘤，也是癌症相关死亡的第二大主要原因。CRC的病因是多因素的，源于基因改变、环境暴露和年龄相关生理变化的复杂相互作用。在众多调节细胞稳态的信号通路中，Wnt/β-连环蛋白信号通路不仅在胚胎发育和细胞增殖中起关键作用，还促成了包括CRC在内的各种恶性肿瘤的发生和发展。Wnt/β-连环蛋白信号通路的失调是CRC的一个标志，在调节化疗耐药性以及驱动侵袭和转移行为方面发挥着关键作用。中医药（TCM）的特点是具有多靶点和多途径作用机制。大量研究表明，中医药可通过靶向Wnt/β-连环蛋白信号通路抑制CRC细胞的活性，并在CRC动物模型中显著缓解症状，证明了其在CRC治疗中的潜在治疗价值。本综述主要关注过去5年从PubMed、Web of Science、Scopus、MEDLINE和Springer等数据库检索到的有关靶向Wnt/β-连环蛋白信号通路治疗CRC的文献。它重点介绍了中药单体（如杨梅素、染料木黄酮、黄芩素）、中药制剂（如排脓散（PNS）、解毒消痈饮（JXY）、左金丸（ZJW））和小分子抑制剂（如PCDHGA9、西妥昔单抗、PTK7）的研究进展。此外，还对这些研究的实验结果和结论进行了深入分析和讨论。通过对文献的全面综述，我们得出结论，中医药在CRC的预防和治疗中表现出多层次、多靶点和多方面的作用。深入研究中医药靶向Wnt/β-连环蛋白信号通路预防和治疗CRC的机制，可能为探索CRC的发病机制和开发CRC的新治疗药物提供新的见解。
