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

    11 Citations (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

    Bibliographical note

    Funding Information:
    This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education [grant number NRF-2019R1I1A3A01061468].

    Publisher Copyright:
    © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

    Keywords

    • Glioblastoma
    • Jagged
    • Notch signalling
    • STAT signalling

    ASJC Scopus subject areas

    • Animal Science and Zoology
    • General Biochemistry,Genetics and Molecular Biology

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