未折叠蛋白反应在胰腺癌发生发展中的作用及意义

胰腺癌是一种致死率相当高的消化系统肿瘤，其起病隐蔽导致早期诊断困难。近期研究发现，内质网应激 (endoplasmic reticulum stress，ERS) 状态下的未折叠蛋白反应 (unfolded protein response，UPR) 通路的调节作用，对于胰腺癌发生发展至关重要。UPR通路伴侣蛋白 GRP78 抑制了胰腺导管腺癌 (pancreatic adenocarcinoma，PDAC)细胞的凋亡，并增强了其化学抗性和耐药性。而 UPR 途径及其调节因子对于血管内皮生长因子 (vascular endothelial growth factor，VEGF) 的调节作用，有助于胰腺癌抵抗缺血缺氧环境。尝试靶向 UPR 途径关键调节因子的药物来控制胰腺癌的研究，可以为胰腺癌的治疗开辟新的途径。本文通过对近年来 UPR 在胰腺癌发生发展中的作用及意义进行综述，希望为通过调控 UPR 通路作为针对治疗胰腺癌的关键过程的一种新型抗癌方法研究提供参考。

The Role and Significance of Unfolded Protein Response in the Development of Pancreatic Cancer

Pancreatic cancer is a kind of digestive system tumor with high mortality rate. Its early diagnosis is difficult due to its concealment. It has been found that the unfolded protein response (UPR) pathway in the endoplasmic reticulum stress (ERS) is crucial for the development of pancreatic cancer in recent years. The UPR pathway chaperone protein GRP78 inhibits the apoptosis of pancreatic cancer cells and enhances the resistance and tolerance to drugs of pancreatic adenocarcinoma (PDAC). The regulation of vascular endothelial growth factor (VEGF) by UPR pathway and its regulatory factors contributes to the resistance of pancreatic cancer to ischemia and hypoxia. Targeted drugs for the key regulators of the UPR pathway will be a new method for the treatment of pancreatic cancer. This article reviews the recent research on the role of UPR in the development of pancreatic cancer, which helps to provide reference for the study of UPR pathway as a novel anticancer method for pancreatic cancer.