Department of Endocrinology, Tianjin First Central Hospital, Tianjin 300192, China.
Clinical Laboratory, Tianjin First Central Hospital, Tianjin 300192, China.
Endocr J. 2019 Dec 25;66(12):1053-1062. doi: 10.1507/endocrj.EJ19-0215. Epub 2019 Aug 30.
In this study, we aim to explore the anti-tumor effect of liraglutide (Lira), an anti-diabetic medicine, on pancreatic cancer cell PANC-1 co-cultured with or without pancreatic stellate cells (PSCs). The chemical count kit-8 and Annexin V-FITC apoptosis detection were conducted to investigate the effect of Lira on cell viability and proliferation of PANC-1 with or without PSCs co-culture. Then, the wound healing and transwell experiments were performed to explore the influence of Lira on PANC-1 cells' migration and invasion capabilities. To identify the potential action mechanism of Lira on PANC-1, the expression of E-cadherin and N-cadherin and the intracellular calcium content in PANC-1, after Lira administration, were detected. The results indicated that Lira in 100 and 1,000 nmol/L, effectively decreased the cell viability and dose-dependently promoted cell apoptosis of PANC-1 co-cultured with or without PSCs. Lira significantly reduced the migration and invasion of PANC-1 and also reduced the inducing effect of PSCs to PANC-1. Lira effectively induced the expression of E-cadherin and suppressed the expression of N-cadherin with a dose-dependent manner. Otherwise, Lira significantly reduced the abnormal high content of calcium in PANC-1 and also weakened the elevation of calcium in PANC-1 induced by cell-cell interaction. The current study firstly indicated that Lira suppressed the cell proliferation, migration and invasion of PANC-1 with or without PSCs co-culture. This effect was partially due to the calcium modulation of Lira and its influence on Ca-binding proteins, such as E-cadherin and N-cadherin.
在这项研究中，我们旨在探索利拉鲁肽（Lira）——一种抗糖尿病药物——对与胰腺星状细胞（PSC）共培养或不共培养的胰腺癌细胞 PANC-1 的抗肿瘤作用。通过化学计数试剂盒-8 和 Annexin V-FITC 凋亡检测，研究 Lira 对 PANC-1 细胞活力和增殖的影响，以及 PSC 共培养的影响。然后，进行划痕愈合和 Transwell 实验，以探讨 Lira 对 PANC-1 细胞迁移和侵袭能力的影响。为了确定 Lira 对 PANC-1 的潜在作用机制，检测了 Lira 给药后 PANC-1 中 E-钙黏蛋白和 N-钙黏蛋白的表达以及细胞内钙含量。结果表明，100 和 1000 nmol/L 的 Lira 有效降低了与或不与 PSCs 共培养的 PANC-1 的细胞活力，并呈剂量依赖性促进细胞凋亡。Lira 显著降低了 PANC-1 的迁移和侵袭能力，也降低了 PSCs 对 PANC-1 的诱导作用。Lira 有效诱导 E-钙黏蛋白的表达，并呈剂量依赖性抑制 N-钙黏蛋白的表达。此外，Lira 显著降低了 PANC-1 中异常高的钙含量，并减弱了细胞-细胞相互作用引起的 PANC-1 中钙的升高。本研究首次表明，Lira 抑制了与或不与 PSCs 共培养的 PANC-1 的细胞增殖、迁移和侵袭。这种作用部分归因于 Lira 对钙的调节及其对钙结合蛋白（如 E-钙黏蛋白和 N-钙黏蛋白）的影响。
