Department of General Surgery, The Second Clinical Medical School of Nanjing Medical University, 210029, Nanjing, Jiangsu, China.
Department of General Surgery, The Second Clinical Medical School of Nanjing Medical University, 210029, Nanjing, Jiangsu, China.
Biochem Biophys Res Commun. 2019 Feb 19;509(4):925-930. doi: 10.1016/j.bbrc.2018.12.182. Epub 2019 Jan 12.
Pancreatic cancer has a poor prognosis. Many epidemiological evidence show that diabetes is closely related to the occurrence of pancreatic cancer. The concentration of insulin in pancreas local tissues is higher than that in systemic circulation. In this study, we aimed to investigate the effect of insulin on pancreatic duct epithelial cells and identify the potential mechanisms. We found that insulin promoted the proliferation of pancreatic duct epithelial cells in the dependent of increased PLK1. Furthermore, PI3K/AKT and NF-κB pathway were involved in this process. By using PI3K/AKT inhibitor LY294002 and NF-κB shRNA, the increased PLK1 was reversed and cells proliferation was inhibited. Additionally, immunofluorescence analysis revealed the co-localization between PLK1 and β-catenin. We showed that insulin can promote the increased expression of β-catenin dependent on PLK1. This study showed that insulin may promotes cell proliferative vitality of pancreatic ductal epithelial cells by inducing PLK1 through PI3K/AKT and NF-κB pathway; The upregulation of PLK1 may reduce the degradation of β-catenin. This may be one of the mechanisms by which T2DM promotes pancreatic cancer.
胰腺癌预后不良。许多流行病学证据表明，糖尿病与胰腺癌的发生密切相关。胰岛素在胰腺局部组织中的浓度高于全身循环中的浓度。在这项研究中，我们旨在研究胰岛素对胰腺导管上皮细胞的影响，并确定潜在的机制。我们发现，胰岛素依赖于 PLK1 的增加促进了胰腺导管上皮细胞的增殖。此外，PI3K/AKT 和 NF-κB 通路参与了这一过程。通过使用 PI3K/AKT 抑制剂 LY294002 和 NF-κB shRNA，逆转了增加的 PLK1，抑制了细胞增殖。此外，免疫荧光分析显示 PLK1 与 β-连环蛋白共定位。我们表明，胰岛素可以通过 PI3K/AKT 和 NF-κB 通路诱导 PLK1 来促进 β-连环蛋白依赖性的表达增加。这项研究表明，胰岛素可能通过 PI3K/AKT 和 NF-κB 通路诱导 PLK1 从而促进胰腺导管上皮细胞的增殖活力；PLK1 的上调可能会减少 β-连环蛋白的降解。这可能是 T2DM 促进胰腺癌的机制之一。
