Combined inhibition of STAT and Notch signalling effectively suppresses tumourigenesis by inducing apoptosis and inhibiting proliferation, migration and invasion in glioblastoma cells

Israt Jahan Tulip, Sung Ok Kim, Eun Jung Kim, Jaebong Kim, Jae Yong Lee, Hyunggee Kim, Sung Chan Kim

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Glioblastoma multiforme (GBM) is the most aggressive primary brain cancer and this is due to cancer cells being apoptosis-resistant and having increased cell proliferation, migration, invasion, and angiogenesis properties. Previous studies have indicated both STAT and Notch pathways being important for initiation and progression in GBM. In this work, we first studied the effects of STAT inhibitors on Notch signalling using small molecule STAT inhibitors. It was observed that STAT inhibitors surprisingly activated Notch signalling by inducing NICD and Notch target genes in GBM cells. Thus, we aimed to combine STAT inhibitor treatment with a Notch pathway inhibitor and study effects on GBM tumourigenesis. STAT5 inhibitor (Pimozide) and STAT3 inhibitor (S3I-201) were individually used in combination with γ-secretase inhibitor (DAPT), an inhibitor of Notch signalling, in a panel of GBM cells for cell proliferation and epithelial plasticity changes. Compared with single-agent treatments, combinatorial treatments with the STAT and Notch inhibitors significantly increased apoptosis in the treated cells, impairing cell proliferation, migration, and invasion. These findings suggest that concurrent blocking of STAT and Notch signalling pathways could provide added therapeutic benefit for the treatment of glioblastoma.

Original languageEnglish
Pages (from-to)161-170
Number of pages10
JournalAnimal Cells and Systems
Volume25
Issue number3
DOIs
Publication statusPublished - 2021

Keywords

  • Glioblastoma
  • Jagged
  • Notch signalling
  • STAT signalling

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Biochemistry, Genetics and Molecular Biology(all)

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