Resveratrol slows the tumourigenesis of pancreatic cancer by inhibiting NFκB activation

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumour with an extremely poor prognosis due to its insidious initiation and a lack of therapeutic strategies. Resveratrol suppresses pancreatic cancer progression and attenuates pancreatitis by modulating multiple targets, including nuclear factor kappa B (NF kappa kappa B) signalling pathways. However, the effect of resveratrol on pancreatic cancer initiation and its mechanisms remain unclear. In this study, we utilised the LSL-Kras(G12D/+); Pdx1-Cre (KC) spontaneous pancreatic precancerous lesion mouse model to explore the anti-tumourigenesis mechanisms of resveratrol in vivo. In vitro acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasias (PanINs) formation assays were performed by pancreatic acinar cell 3-dimensional (3D) culture. Histopathological analysis was used to examine the pathological morphology of pancreatic tissues. Resveratrol prevented the progression of pancreatic precancerous lesions and inhibited the activation of NF kappa B signalling pathway-related molecules in KC mouse pancreatic tissues. In addition, resveratrol reduced the severity of cerulein-induced pancreatitis and the formation of ADM/PanINs in vivo and in vitro, which may be related to its effect on NF kappa B inactivation. Furthermore, pancreatic acinar 3D culture demonstrated that activation of the NF kappa B signalling pathway promoted the formation of ADM/PanINs in vitro, and this initiating effect of NF kappa B was blocked by resveratrol. Resveratrol slowed the tumourigenesis of pancreatic cancer by inhibiting NF kappa B activation.