肺癌是临床最常见的呼吸系统恶性肿瘤，其发病率与死亡率均位居全球恶性肿瘤首位。当前肺癌临床治疗以手术、放疗、化疗、靶向治疗及免疫治疗为主，但受限于术后高复发率、治疗相关不良反应及多重耐药等问题制约，整体疗效仍不理想，亟需进一步优化与探索新的治疗策略。刺猬（Hedgehog）信号通路在肺癌中呈异常激活状态，可通过自分泌与旁分泌环路驱动肿瘤恶性表型，进而促进肿瘤侵袭、转移及多药耐药的发生发展，故靶向抑制该通路已成为肺癌治疗的重要研究方向。中医药具备整体调控、多靶点、多层次干预的抗肿瘤核心优势，可通过抑制肿瘤增殖、减轻并发症、提升综合疗效等方式发挥抗肺癌效应，现已成为肺癌临床综合防治体系中的重要组成部分。研究表明，皂苷类、生物碱类、萜类、黄酮类等多种中药活性成分和衍生物，半枝莲甲醇提取物、冬虫夏草乙醇提取物、睡茄乙醇提取物等中药提取物以及二陈汤、醒消丸、补肾疏肝方、温下方等中药复方均能有效调控Hedgehog信号通路及其交叉互作网络，进而通过诱导肺癌细胞自噬与凋亡、抑制肿瘤血管生成、削弱肿瘤干细胞特性、阻滞上皮-间质转化、逆转耐药表型及调控细胞周期等多重途径发挥抗肺癌效应。系统梳理近5年中医药调控Hedgehog信号通路治疗肺癌的作用机制，以期为临床抗肺癌新药研发与治疗方案优化提供思路与参考。

Lung cancer is the most common respiratory malignancy in clinical practice, with both its incidence and mortality ranking first among all malignant tumors worldwide. Current clinical treatments for lung cancer primarily include surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. However, the overall efficacy remains unsatisfactory due to challenges such as high postoperative recurrence rates, treatment-related adverse reactions, and multidrug resistance. There is an urgent need to further optimize existing strategies and explore novel therapeutic approaches. The Hedgehog signaling pathway is aberrantly activated in lung cancer and drives malignant phenotypes through autocrine and paracrine loops, thereby promoting tumor invasion, metastasis, and the development of multidrug resistance. Therefore, targeted inhibition of this pathway has become an important research direction in lung cancer therapy. Traditional Chinese medicine (TCM) possesses core advantages in antitumor therapy, including holistic regulation, multi-target and multi-level intervention. TCM exerts anti-lung cancer effects by inhibiting tumor proliferation, alleviating complications, and improving overall treatment outcomes, and has become an integral part of comprehensive clinical management of lung cancer. Studies have shown that various active ingredients and derivatives from Chinese herbs, such as saponins, alkaloids, terpenoids, and flavonoids; herbal extracts including Scutellaria barbata methanol extract, Cordyceps sinensis ethanol extract, and Withania somnifera ethanol extract; as well as TCM formulas such as Erchen Decoction, Xingxiao Pill, Bushen Shugan Formula, and Wenxia Formula, can effectively regulate the Hedgehog signaling pathway and its crosstalk networks. They exert anti-lung cancer effects through multiple mechanisms, including inducing autophagy and apoptosis of lung cancer cells, inhibiting tumor angiogenesis, suppressing cancer stem cell properties, blocking epithelial-mesenchymal transition, reversing drug-resistant phenotypes, and regulating the cell cycle. Systematically review the mechanisms by which TCM regulates the Hedgehog signaling pathway in the treatment of lung cancer over the past five years, aiming to provide insights and references for the development of new anti-lung cancer drugs and optimization of therapeutic strategies.

R285.5

国家自然科学基金资助项目（82505540）；河南省中医药科学研究专项（2025ZY3047）