Resveratrol Exerts Antitumor Effects on Pancreatic Cancer by Inhibiting Notch Signaling Induced by Chronic Stress

Abstract

Abstract Resveratrol is a natural polyphenolic compound found in plants that has a variety of pharmaceutical uses. However, its molecular mechanisms in tumor progression are not fully understood. Chronic stress refers to the nonspecific systemic reaction that occurs when the body is stimulated by various internal and external negative factors over a long time. Chronic stress and its related hormones epinephrine and norepinephrine (NE) play a crucial role in tumor progression. Currently, the exact role of chronic stress in pancreatic cancer is unknown. The Notch signaling pathway plays an important role in pancreatic carcinogenesis. The present study focuses on the effect of resveratrol on NE-induced pancreatic cancer progression. The results indicate that NE could induce acinar cell conversion into acinar-to-ductal metaplasia (ADM). Furthermore, we found that NE enhanced pancreatic cancer cell proliferation, migration and invasion in vitro and promoted Notch1 protein expression. In addition, resveratrol inhibited pancreatic cancer by suppressing chronic stress-mediated Notch signaling. Overall, our study suggests that resveratrol may serve as an effective adjuvant therapy for the treatment of pancreatic cancer.