The inhibitory effect of 5,7-DMF on pancreatic sphere-forming cell function mediated by FoxM1 gene expression

J Cell Biochem. 2018 Feb;119(2):1855-1865. doi: 10.1002/jcb.26346. Epub 2017 Oct 27.

Abstract

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.

Keywords: 5,7-DMF; FoxM1; Sox2; pancreatic cancer; sphere-forming cell; stem cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation
  • Drug Screening Assays, Antitumor
  • Epithelial-Mesenchymal Transition
  • Flavonoids / pharmacology*
  • Forkhead Box Protein M1 / genetics*
  • Forkhead Box Protein M1 / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • SOXB1 Transcription Factors / genetics*
  • SOXB1 Transcription Factors / metabolism
  • Spheroids, Cellular / drug effects*
  • Spheroids, Cellular / metabolism

Substances

  • FOXM1 protein, human
  • Flavonoids
  • Forkhead Box Protein M1
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • 5,7-dimethoxy-4'-hydroxyflavone