现代药理学研究证实，肿瘤微环境缺氧可诱导缺氧诱导因子-1α（HIF-1α）异常高表达。高表达的HIF-1α可进一步上调血管内皮生长因子（VEGF）等多种促血管生成因子，进而加速肿瘤新生血管形成。HIF-1α/VEGF信号通路是调控肿瘤恶性演进的核心通路，该通路可通过介导肿瘤血管新生、推动肿瘤增殖与远处转移、重塑肿瘤能量代谢、介导肿瘤免疫逃逸、诱导肿瘤化疗耐药以及维持肿瘤干细胞干性等多重途径，加快肿瘤恶性进展。目前，以HIF-1α/VEGF通路为靶点的贝伐珠单抗、索拉非尼等临床靶向抗肿瘤药物已展现出明确治疗效果，但这类药物存在不良反应明显、单靶点干预易继发获得性耐药等。近年来大量研究证实，中药单体、有效提取物及中药复方具备多成分、多靶点、多通路协同作用、低不良反应的独特优势，可通过下调HIF-1α与VEGF蛋白及基因表达，阻断肿瘤新生血管生成，进而抑制肿瘤发生、发展与转移。围绕HIF-1α/VEGF信号通路，系统梳理近年来中药单体、提取物及中药复方干预该通路发挥抗肿瘤作用的最新研究进展，旨在为肿瘤抗血管生成治疗提供新的理论参考与临床研发思路。

Modern pharmacological studies have confirmed that hypoxia in the tumor microenvironment can induce abnormal overexpression of hypoxia-inducible factor-1α (HIF-1α). Overexpressed HIF-1α further upregulates various pro-angiogenic factors, including vascular endothelial growth factor (VEGF), thereby accelerating the formation of tumor neovasculature. The HIF-1α/VEGF signaling pathway is a central route regulating malignant progression of tumors. This pathway promotes tumor malignancy through multiple mechanisms, such as mediating tumor angiogenesis, driving tumor proliferation and distant metastasis, remodeling tumor energy metabolism, facilitating immune evasion, inducing chemoresistance, and maintaining cancer stem cell properties. Currently, clinical targeted anti-tumor drugs targeting the HIF-1α/VEGF pathway-such as bevacizumab and sorafenib-have demonstrated clear therapeutic efficacy; however, these agents are associated with significant adverse effects and a high risk of acquired resistance due to single-target intervention. In recent years, numerous studies have shown that individual herbal compounds, active extracts, and traditional Chinese medicine (TCM) formulae possess unique advantages, including multi-component, multi-target, and multi-pathway synergistic effects along with low toxicity. These TCM agents can downregulate the expression of HIF-1α and VEGF at both protein and gene levels, block tumor neovascularization, and thereby inhibit tumor initiation, progression, and metastasis. This review systematically summarizes recent advances in research on the anti-tumor effects of individual TCM compounds, extracts, and formulae targeting the HIF-1α/VEGF signaling pathway, aiming to provide new theoretical insights and clinical development strategies for antiangiogenic cancer therapy.

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国家自然科学基金资助项目（82204981）；河南省特色骨干学科中医学学科建设项目（STG-ZYX06-202145）；河南省中医药科学研究专项课题（2021JDZX2002）；河南省中医药科学研究专项课题（20-21ZY2115）；河南省中医院博士科研基金（2022BSJJ07）；河南省中医院博士科研基金（2023BSJJ02）；河南中医药大学2022年度研究生科研创新能力提升计划项目（2022KYCX057）；河南中医药大学2024年度研究生科研创新能力提升计划项目（2024SHDY011）