Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea.
Division of Gastroenterology, Department of Internal Medicine, Catholic Kwandong University, International St. Mary's Hospital, Incheon 22711, Republic of Korea.
Oncol Rep. 2017 Dec;38(6):3632-3638. doi: 10.3892/or.2017.6045. Epub 2017 Oct 19.
Reactive oxygen species (ROS) play a key role in cancer development and progression. Ursodeoxycholic acid (UDCA) may possess antioxidant, anti-inflammatory and chemoprophylatic effects. Therefore, we aimed to investigate the effects and mechanisms of UDCA treatment on pancreatic cancer cells. The pancreatic cancer cell lines HPAC and Capan-1 were treated with 0.2 mM UDCA. To examine alterations in the levels of intracellular ROS, the DCF-DA stain was used and both stemness and epithelial-mesenchymal transition (EMT)-related genes were quantified using qRT-PCR and western blot analysis. The pancreatic cancer sphere culture was performed following seven days of treatment with 0.2 mM UDCA, as an indicator of stemness. Following treatment with UDCA, the level of intracellular ROS was decreased in the pancreatic cancer cells. UDCA decreased both the phosphorylation of STAT3 and the expression of peroxiredoxin II (Prx2). Furthermore, the treatment resulted in the upregulation of E-cadherin and in the downregulation of N-cadherin. In addition, UDCA decreased the expression of sex determining region Y-box 2 (Sox2) and it diminished the number of pancreatic cancer spheres formed. In conclusion UDCA suppressed the levels of intracellular ROS and Prx2 and it decreased EMT and stem cell formation in pancreatic cancer cells. Therefore, UDCA may provide favorable therapeutic benefits, through its antioxidant effects, for patients with pancreatic cancer.
活性氧（ROS）在癌症的发生和发展中起关键作用。熊去氧胆酸（UDCA）可能具有抗氧化、抗炎和化学预防作用。因此，我们旨在研究 UDCA 治疗对胰腺癌细胞的作用和机制。用 0.2mM UDCA 处理胰腺癌细胞系 HPAC 和 Capan-1。为了检测细胞内 ROS 水平的变化，使用 DCF-DA 染色，并通过 qRT-PCR 和 Western blot 分析定量测定干性和上皮-间充质转化（EMT）相关基因。用 0.2mM UDCA 处理 7 天后进行胰腺癌细胞球培养，作为干性的指标。用 UDCA 处理后，胰腺癌细胞内的 ROS 水平降低。UDCA 降低了 STAT3 的磷酸化和过氧化物酶 II（Prx2）的表达。此外，该治疗导致 E-钙粘蛋白的上调和 N-钙粘蛋白的下调。此外，UDCA 降低了性别决定区 Y 框 2（Sox2）的表达，并减少了形成的胰腺癌细胞球的数量。总之，UDCA 抑制了细胞内 ROS 和 Prx2 的水平，并降低了胰腺癌细胞的 EMT 和干细胞形成。因此，UDCA 通过其抗氧化作用可能为胰腺癌患者提供有利的治疗益处。
