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1.陕西中医药大学,陕西 咸阳 712046
2.陕西中医药大学 附属医院,陕西 咸阳 712000
3.常州市中医医院,江苏 常州 213000
4.咸阳市中心医院,陕西 咸阳 712000
5.上海中医药大学 曙光医院,上海 200021
Received:12 August 2024,
Accepted:06 March 2025,
Published Online:11 October 2024,
Published:20 July 2025
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申佳林,赵小莹,薛成成等.中药靶向Wnt信号通路防治结直肠癌研究进展[J].中国实验方剂学杂志,2025,31(14):303-314.
SHEN Jialin,ZHAO Xiaoying,XUE Chengcheng,et al.Prevention and Treatment of Colorectal Cancer Through Traditional Chinese Medicine Targeted Wnt Signaling Pathway: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2025,31(14):303-314.
申佳林,赵小莹,薛成成等.中药靶向Wnt信号通路防治结直肠癌研究进展[J].中国实验方剂学杂志,2025,31(14):303-314. DOI: 10.13422/j.cnki.syfjx.20242325.
SHEN Jialin,ZHAO Xiaoying,XUE Chengcheng,et al.Prevention and Treatment of Colorectal Cancer Through Traditional Chinese Medicine Targeted Wnt Signaling Pathway: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2025,31(14):303-314. DOI: 10.13422/j.cnki.syfjx.20242325.
Wnt/
β
-连环蛋白(
β
-catenin)信号通路与肠道、骨骼、神经等多个组织的发育和更新有关,然而,其异常激活可以导致多种肿瘤的发生和发展,其中与结直肠癌(CRC)的关系最为密切。超过93%的CRC患者在Wnt/
β
-catenin通路基因中至少有一个突变,因此靶向Wnt信号通路对于CRC的防治有着巨大的潜力。临床上中医药已经广泛地用于CRC的全程治疗中,也取得了较好的疗效,近年来,大量研究表明中药可以通过多靶点调控Wnt/
β
-catenin信号通路来防治CRC。但缺乏系统的总结和综述。因此,该文通过检索PubMed、中国知网(CNKI)数据库2015年至2024年的相关文献,系统总结了中药单体(如小檗碱、人参皂苷、姜黄素、吴茱萸碱等)和中药复方(如四君子汤、黄芩汤、乌梅丸等)通过调控Wnt信号通路防治CRC的研究进展。这些研究表明,中药可以通过靶向Wnt及其膜受体(如Wnt3a等)、靶向降解复合物[如轴抑制蛋白(AXIN)和糖原合成酶激酶-3
β
(GSK-3
β
)等]和靶向转录复合物[如
β
-catenin与T细胞因子/淋巴样增强因子(TCF/LEF)]这3个方面,来抑制Wnt通路靶基因[如c-Myc、基质金属蛋白酶(MMPs)等]的激活,发挥抑制CRC的增殖、耐药和侵袭转移的作用。该文还讨论了目前研究存在的不足,如部分中药口服利用度低、缺乏临床有效性和安全性验证等问题。展望多组学联合、基因编辑技术在中药调控Wnt信号通路研究中的前景,以期为中药抗CRC机制研究及靶向Wnt通路抗CRC新药的研发和临床应用提供参考依据。
The Wnt/
β
-catenin signaling pathway is associated with the development and regeneration of tissue, including intestines, bones, and nerves. However, its aberrant activation leads to the onset and progression of multiple tumors, among which colorectal cancer (CRC) is most closely linked to it. At least one mutation in genes associated with the Wnt/
β
-catenin pathway can be observed in over 93% of CRC patients, and thus targeting the pathway holds substantial potential for CRC prevention and treatment. Clinically, traditional Chinese medicine (TCM) has been widely applied to the full-course treatment of CRC, yielding promising outcomes. Recent studies have demonstrated that TCM can inhibit CRC through multi-target modulation of the Wnt/
β
-catenin signaling pathway. However, there is a lack of a systematic review of these findings. This review summarized the research progress on the use of TCM monomers (such as berberine, ginsenos
ides, curcumin, and evodiamine) and compound formulas (such as Si Junzitang, Huangqintang, and Wumeiwan) in the prevention and treatment of CRC by regulating the Wnt signaling pathway, based on literature from PubMed and China National Knowledge Infrastructure (CNKI) databases between 2015 and 2024. These studies indicated that TCM could inhibit the activation of Wnt pathway target genes, such as c-Myc and matrix metalloproteinases (MMPs) by targeting Wnt ligands and their receptors (such as Wnt3a), the destruction complex, such as Axis suppressor protein(AXIN) and glycogen synthase kinase-3
β
(GSK-3
β
), and the transcriptional complex,such as
β
-catenin and T-cell factor/lymphoid enhancer-binding factor (TCF/LEF). Through these mechanisms, TCM exerted inhibitory effects on CRC proliferation, drug resistance, and invasion and metastasis. Additionally, the review discussed current research gaps, such as the low oral availability of some TCMs and the lack of clinical validation for efficacy and safety. The prospects of integrating multi-omics and gene editing technologies into the study of TCM's modulation of the Wnt signaling pathway were also explored. Ultimately, the review aims to provide a reference for research on the mechanisms of TCM in CRC prevention and treatment, as well as the development and clinical application of novel anti-CRC drugs targeting the Wnt pathway.
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