二肽基肽酶4抑制剂与2型糖尿病患者肿瘤发生的关联研究进展

Advances in the Association between Dipeptidyl Peptidase 4 Inhibitors and Tumorigenesis in Type 2 Diabetes Mellitus

摘要: 二肽基肽酶4 (Dipeptidyl Peptidase, DPP4)是一种广泛表达的丝氨酸蛋白酶，通过酶促作用调控多种生物活性肽(如肠促胰素、趋化因子)的活性，其抑制剂(二肽基肽酶4抑制剂)已广泛用于2型糖尿病的治疗。DPP4抑制剂作为临床广泛应用的口服降糖药，通过抑制DPP4酶活性，延长肠促胰素(如胰高血糖素样肽-1)的半衰期，从而实现血糖调控。其独特的作用机制不仅局限于代谢调节，还可能通过影响肿瘤细胞信号通路、免疫微环境等途径参与肿瘤发生与发展。近年来，DPP4抑制剂对肿瘤发生的影响成为研究热点，但其作用呈现双重性：在部分肿瘤中表现为促癌效应，而在另一些肿瘤中则显示出抑癌潜力。本文基于现有文献，系统综述DPP4抑制剂对肿瘤发生的影响机制、在不同肿瘤类型中的作用差异及临床研究证据，同时探讨其临床应用的潜在风险与前景，为肿瘤与糖尿病领域的交叉研究及临床决策提供参考。

Abstract: Dipeptidyl peptidase 4 (DPP4) is a widely expressed serine protease that regulates the activity of various bioactive peptides, such as incretins and chemokines, via enzymatic catalysis. Its inhibitors (Dipeptidyl Peptidase 4 Inhibitor) have been widely used in the treatment of type 2 diabetes mellitus. As commonly prescribed oral hypoglycemic agents in clinical practice, DPP4 inhibitors exert glucose-regulating effects by inhibiting the enzymatic activity of DPP4 and prolonging the half-life of incretins such as glucagon-like peptide-1. Beyond metabolic regulation, their unique mechanism of action may also participate in tumorigenesis and tumor progression by modulating tumor cell signaling pathways and the immune microenvironment. In recent years, the impact of DPP4 Inhibitor on tumorigenesis has become a research hotspot. However, their effects are dualistic: they show pro-tumorigenic effects in some tumors but anti-tumor potential in others. Based on current literature, this review systematically summarizes the mechanisms underlying the effects of DPP4 inhibitors on tumorigenesis, the divergent roles in different tumor types, and relevant clinical evidence. It also discusses the potential risks and prospects of their clinical application, aiming to provide a reference for interdisciplinary research and clinical decision-making in oncology and diabetes.