TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000651671
  • Gene Name:NOTCH1
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:NA
  • Evidence:predicted
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:NA
  • Drug Method:NA

Disease basic infommation

  • Disease:osteosarcoma
  • Tissue:Human osteosarcoma cell lines including 143B, U2OS, MG63, G292 and ZOS

Other information

  • Title:Tideglusib suppresses stem-cell-like features and progression of osteosarcoma by inhibiting GSK-3β/NOTCH1 signaling.
  • Journal:Biochemical and biophysical research communications
  • Published:2021
  • PubMed ID:33813076
  • Abstract:Osteosarcoma is the most common primary bone tumor in children, teenagers and adolescents. Cancer stem cells (CSCs) have the function to self-renew and keep the phenotype of tumor, causing clinical treatment failure. Therefore, developing effective therapies to inhibit osteosarcoma progression is urgently necessary. Glycogen synthase kinase 3β (GSK-3β)is highly expressed in osteosarcoma. In the present study, we made an exploration on the anti-tumor effect of tideglusib (TID), a small-molecule inhibitor of GSK-3β, and revealed the underlying mechanisms. Here, we found that TID markedly reduced the cell viability of different osteosarcoma cell lines. Cell cycle arrest distributed in G2/M was markedly up-regulated in TID-incubated osteosarcoma cells through enhancing p21 expression levels. Apoptosis was evidently induced in osteosarcoma cells via blocking Caspase-3 activation. Consistently, tumor growth was effectively suppressed in an established murine xenograft model with few toxicity and side effects in vivo. Furthermore, TID markedly repressed stem-cell-like activity in osteosarcoma cells through down-regulating NOTCH1 expression. Notably, rescuing NOTCH1 significantly abolished the role of TID in reducing cell proliferation and sarcosphere-formation. Mechanistically, we found that TID-inhibited NOTCH1 expression was associated with the blockage of AKT/GSK-3β signaling pathway. In summary, we for the first time provided evidence that TID could effectively inhibit osteosarcoma progression through repressing cell proliferation, inducing apoptosis, suppressing stem-cell-like properties via down-regulating AKT/GSK-3β/NOTCH1 signaling pathway. Thus, TID may be a promising therapeutic strategy for osteosarcoma treatment without side effects.
@Copyright Harbin Medical University
　The 2nd Affiliated Hospital of Harbin Medical University
　 备案号：鲁ICP备2022025566号-3