Department of Digestive Oncology, Affiliated Tumor Hospital of Central South University, Changsha, Hunan Province, P. R. China.
Institute of Oncology, Central South University, Changsha, P. R. China.
J Cell Biochem. 2018 Feb;119(2):1855-1865. doi: 10.1002/jcb.26346. Epub 2017 Oct 27.
Pancreatic cancer is one of the major human malignant tumors severely endangering human health and life with high mortality due to the concealment of early symptoms and lack of effective therapies during advanced stages. The identification of pancreatic cancer stem cell functions has been as important strategy for understanding of pancreatic cancer biology and novel drug and therapy development. In the present study, we successfully isolated the pancreatic sphere-forming cells from pancreatic cancer cell line PANC-1 by sphere-forming method and we found that the sphere-forming ability and the cell migration rate of pancreatic sphere-forming cells were significantly inhibited by 5,7-DMF treatment, which was supported by the corresponding changes of several EMT biomarkers after being treated with 5,7-DMF. Moreover, we revealed here that the inhibition of pancreatic sphere-forming cells was mediated by the expression of FoxM1 gene, and also the expression of SOX2 gene was regulated by FoxM1 in pancreatic sphere-forming cells and involved in the inhibitory role of 5,7-DMF. These results provided important basis for the application of 5,7-DMF as a novel drug candidate for the pancreatic cancer treatment.
胰腺癌是严重威胁人类健康和生命的人类主要恶性肿瘤之一，由于早期症状隐匿，晚期缺乏有效治疗方法，死亡率较高。鉴定胰腺癌干细胞功能一直是理解胰腺癌生物学和新药物及治疗方法发展的重要策略。在本研究中，我们通过球体形成方法成功地从胰腺癌细胞系 PANC-1 中分离出胰腺球体形成细胞，我们发现 5,7-DMF 处理显著抑制胰腺球体形成细胞的球体形成能力和细胞迁移率，这得到了用 5,7-DMF 处理后几个 EMT 生物标志物相应变化的支持。此外，我们在这里揭示了胰腺球体形成细胞的抑制是由 FoxM1 基因的表达介导的，并且 Sox2 基因的表达也受到 FoxM1 在胰腺球体形成细胞中的调节，并参与了 5,7-DMF 的抑制作用。这些结果为将 5,7-DMF 作为治疗胰腺癌的新型候选药物提供了重要依据。
