Resveratrol slows the tumourigenesis of pancreatic cancer by inhibiting NFκB activation - 30/05/20
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Graphical abstract |
Highlights |
• | Resveratrol decelerated the severity of pancreatic precancerous lesions. |
• | Resveratrol reduced the cerulein induced pancreatitis mediated pancreatic cancer initiation. |
• | Resveratrol inhibited NFκB singling pathway of pancreatic precancerous lesions in vivo. |
• | Resveratrol prevented the formation of in vitro ADM via inhibiting NFκB in acinar cells 3D culture. |
Abstract |
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 (NFκB) signalling pathways. However, the effect of resveratrol on pancreatic cancer initiation and its mechanisms remain unclear. In this study, we utilised the LSL-KrasG12D/+; 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 NFκB 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 NFκB inactivation. Furthermore, pancreatic acinar 3D culture demonstrated that activation of the NFκB signalling pathway promoted the formation of ADM/PanINs in vitro, and this initiating effect of NFκB was blocked by resveratrol. Resveratrol slowed the tumourigenesis of pancreatic cancer by inhibiting NFκB activation.
Le texte complet de cet article est disponible en PDF.Keywords : pancreatic ductal adenocarcinoma, resveratrol, nuclear factor kappa B, tumourigenesis
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Vol 127
Article 110116- juillet 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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