Sun Siyuan, Yu Wenqian, Zhang Guangheng, Li Xiangyu, Song Linjing, Lv Yehan, Chen Yi
Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China.
Front Pharmacol. 2025 Feb 18;16:1548672. doi: 10.3389/fphar.2025.1548672. eCollection 2025.
Gastric cancer (GC) is a prevalent malignant tumor that originates from the epithelial cells of the gastric mucosa, predominantly in the form of adenocarcinoma. Extensive research has confirmed the significant role of autophagy in the initiation, progression, and chemoresistance of GC. The potential of traditional Chinese medicine (TCM) to exert anti-tumor effects by modulating autophagy has been demonstrated, particularly in the context of GC prevention and treatment. Natural products (NPs) have great therapeutic potential in the prevention and treatment of GC by targeting autophagy-related genes and signaling pathways to intervene in the biological behaviors of gastric cancer cells such as proliferation, metastasis, invasion and death. This article describes the molecular mechanisms and key markers of tumor autophagy, the signaling pathways involved in GC-associated autophagy (PI3K/AKT/mTOR, AMPK, MAPK, p53), and summarizes the mechanism of autophagy and infection in GC, how autophagy interacts with apoptotic and iron-death processes and the wide-ranging influences that these factors play in the process. Finally, this paper systematically summarizes the natural compounds of terpenoids, polyphenols, alkaloids, saponins, and polysaccharides that modulate autophagy-related signaling pathways and potential targets for the treatment of GC, and evaluates the toxic effects of NPs, providing a more compelling rationale and direction for GC therapy.
胃癌（GC）是一种常见的恶性肿瘤，起源于胃黏膜上皮细胞，主要为腺癌形式。大量研究已证实自噬在胃癌的发生、发展及化疗耐药中起重要作用。中药通过调节自噬发挥抗肿瘤作用的潜力已得到证实，尤其是在胃癌的预防和治疗方面。天然产物通过靶向自噬相关基因和信号通路干预胃癌细胞的增殖、转移、侵袭和死亡等生物学行为，在胃癌的预防和治疗中具有巨大的治疗潜力。本文阐述了肿瘤自噬的分子机制和关键标志物、与胃癌相关自噬涉及的信号通路（PI3K/AKT/mTOR、AMPK、MAPK、p53），总结了胃癌中自噬与感染的机制、自噬如何与凋亡和铁死亡过程相互作用以及这些因素在该过程中所起的广泛影响。最后，本文系统总结了调节自噬相关信号通路的萜类、多酚类、生物碱类、皂苷类和多糖类天然化合物以及胃癌治疗的潜在靶点，并评估了天然产物的毒性作用，为胃癌治疗提供更有说服力的理论依据和方向。
