摘要
缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)是肿瘤缺氧微环境中的核心转录调控因子,在结直肠癌的发生、发展与转移中发挥关键作用,已成为重要的治疗靶点。中医药可多靶点、多通路协同调控HIF-1α信号通路,在结直肠癌转移的防治中具有独特优势,具体表现为黄芪多糖等中药活性成分、姜黄素等单体及健脾解毒方等复方均可靶向HIF-1α/PD-L1、HIF-1α/VEGF、HIF-1α/PI3K/AKT/mTOR、HIF-1α/ROS、HIF-1α/NF-κB等信号通路,发挥抑制肿瘤细胞增殖、侵袭与转移,阻断血管生成,逆转代谢重编程,改善氧化应激与炎性微环境,诱导细胞凋亡等多重作用。目前中医药调控HIF-1α抗结直肠癌的研究仍面临以下问题:作用机制缺乏系统性整合,研究多集中于单一通路或分子靶点;多数研究停留在细胞与动物实验阶段,缺乏高质量临床研究数据支持;复方多成分的协同与拮抗机制尚不明确。未来需整合系统生物学、多组学、类器官模型研究方法,系统揭示中药复方调控HIF-1α信号网络的整体机制,深入探索中药天然产物在不同疾病背景下的靶向调控规律,从而实现对HIF-1α通路更加精准、安全的干预,构建高效的综合治疗体系。
Hypoxia-inducible factor-1α(HIF-1α)is a key transcriptional regulator in the hypoxic tumor microenvironment and plays a critical role in the occurrence,development,and metastasis of colorectal cancer,making it an important therapeutic target.Traditional Chinese medicine(TCM)can synergistically regulate the HIF-1αsignaling pathway through multiple targets and pathways,offering unique advantages in the prevention and treatment of colorectal cancer metastasis.Specifically,bioactive components of TCM such as astragalus polysaccharides,monomers like curcumin,and compound prescriptions like Jianpi Jiedu decoction can target HIF-1α/PD-L1,HIF-1α/VEGF,HIF-1α/PI3K/AKT/mTOR,HIF-1α/ROS,HIF-1α/NF-κB,and other signaling pathways.These interventions inhibit tumor cell proliferation,invasion,and metastasis,block angiogenesis,reverse metabolic reprogramming,improve oxidative stress and inflammatory microenvironments,and induce apoptosis,among other effects.Currently,research on TCM regulation of HIF-1αagainst colorectal cancer faces several challenges:the mechanisms of action lack systematic integration,studies often focus on single pathways or molecular targets;most research is limited to cell and animal experiments without high-quality clinical data;the synergistic and antagonistic mechanisms of multicomponent formulations are still unclear.Future research should integrate systems biology,multi-omics,and organoid model approaches to systematically reveal the overall mechanisms by which TCM formulations regulate the HIF-1αsignaling network,and deeply explore the targeted regulatory patterns of natural TCM products in different disease contexts.This will facilitate more precise and safe interventions in the HIF-1αpathway and help establish efficient integrated therapeutic systems.
作者
郝姗姗
王遥
王培基
唐宇飞
原钰欣
朱思维
侯风刚
HAO Shanshan;WANG Yao;WANG Peiji;TANG Yufei;YUAN Yuxin;ZHU Siwei;HOU Fenggang(First Clinical Medical College of Shaanxi University of Chinese Medicine,Xianyang Shaanxi China 712046;Shanghai Municipal Hospital of Traditional Chinese Medicine,Shanghai University of Chinese Medicine,Shanghai China 200071;Department of Integrative Medicine,Zhongshan Hospital,Fudan University,Shanghai China 200032)
出处
《中医学报》
2026年第2期322-336,共15页
Acta Chinese Medicine
基金
国家自然科学基金项目(82174188,82374253)
国家自然科学青年基金项目(82205207)。
