Liao Wenhao, Wang Jing, Li Yuchen
Department of Nephrology, the Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, China.
Department of Obstetrics and Gynecology, Chongqing Bishan Hospital of Traditional Chinese Medicine, Chongqing, 402760, China.
J Pharm Anal. 2025 Feb;15(2):101075. doi: 10.1016/j.jpha.2024.101075. Epub 2024 Aug 19.
Gastric carcinoma (GC) is a malignancy with multifactorial involvement, multicellular regulation, and multistage evolution. The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation of the gastric mucosa, in which normal gastric mucosa gradually progresses from inactive or chronic active gastritis (Phase I) to gastric precancerous lesions (Phase II) and finally to GC (Phase III). Correa's cascade highlights the evolutionary pattern of GC and the importance of early intervention to prevent malignant transformation of the gastric mucosa. Intervening in early gastric mucosal lesions, i.e., Phase I and II, will be the key strategy to prevent and treat GC. Natural products (NPs) have been an important source for drug development due to abundant sources, tremendous safety, and multiple pharmacodynamic mechanisms. This review is the first to investigate and summarize the multi-step effects and regulatory mechanisms of NPs on the Correa's cascade in gastric carcinogenesis. In phase I, NPs modulate urease activity, motility, adhesion, virulence factors, and drug resistance, thereby inhibiting -induced gastric mucosal inflammation and oxidative stress, and facilitating ulcer healing. In Phase II, NPs modulate multiple pathways and mediators regulating gastric mucosal cell cycle, apoptosis, autophagy, and angiogenesis to reverse gastric precancerous lesions. In Phase III, NPs suppress cell proliferation, migration, invasion, angiogenesis, and cancer stem cells, induce apoptosis and autophagy, and enhance chemotherapeutic drug sensitivity for the treatment of GC. In contrast to existing work, we hope to uncover NPs with sequential therapeutic effects on multiple phases of GC development, providing new ideas for gastric cancer prevention, treatment, and drug development.
胃癌（GC）是一种涉及多因素、多细胞调控和多阶段演变的恶性肿瘤。经典的科雷亚（Correa）肠型胃癌级联反应明确了胃黏膜恶性转化的三部曲，即正常胃黏膜从非活动性或慢性活动性胃炎（阶段I）逐渐发展为胃癌前病变（阶段II），最终发展为胃癌（阶段III）。科雷亚级联反应突出了胃癌的演变模式以及早期干预以预防胃黏膜恶性转化的重要性。干预早期胃黏膜病变，即阶段I和II，将是预防和治疗胃癌的关键策略。天然产物（NPs）因其来源丰富、安全性高和多种药效学机制，一直是药物开发的重要来源。本综述首次研究并总结了天然产物对胃癌发生中科雷亚级联反应的多步骤作用和调控机制。在阶段I，天然产物调节尿素酶活性、运动性、黏附性、毒力因子和耐药性，从而抑制幽门螺杆菌诱导的胃黏膜炎症和氧化应激，并促进溃疡愈合。在阶段II，天然产物调节多个调控胃黏膜细胞周期、凋亡、自噬和血管生成的途径和介质，以逆转胃癌前病变。在阶段III，天然产物抑制细胞增殖、迁移、侵袭、血管生成和癌症干细胞，诱导凋亡和自噬，并增强化疗药物敏感性以治疗胃癌。与现有研究不同的是，我们希望发现对胃癌发展多个阶段具有序贯治疗作用的天然产物，为胃癌的预防、治疗和药物开发提供新思路。
