These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Napabucasin, a novel inhibitor of STAT3, inhibits growth and synergises with doxorubicin in diffuse large B-cell lymphoma.
    Author: Li X, Wei Y, Wei X.
    Journal: Cancer Lett; 2020 Oct 28; 491():146-161. PubMed ID: 32798587.
    Abstract:
    Diffuse large B-cell lymphoma (DLBCL), the most common type of aggressive non-Hodgkin lymphoma (NHL), has highly heterogeneous molecular characteristics. Although some patients initially respond to standard R-CHOP therapy, 30-40% develop refractory disease or suffer relapse. Signal transducer and activator of transcription 3 (STAT3), which regulates multiple oncogenic processes, has been found to be constitutively activated in various cancers, including DLBCL, suggesting its potential as a therapeutic target. In this study, we determined that 34% (23/69) of DLBCL patients expressed pSTAT3 (Y705) in tumour tissues. Napabucasin, a novel STAT3 inhibitor, exhibited potent cytotoxicity against NHL cell lines in a dose-dependent manner. Mechanistic studies demonstrated that napabucasin induced intrinsic and extrinsic cell apoptosis, downregulated the expression of STAT3 target genes, including the antiapoptotic protein Mcl-1, and regulated the ROS-mediated mitogen-activated protein kinase (MAPK) pathway. Most importantly, in vivo studies revealed the suppressive efficacy of napabucasin as a monotherapy without obvious toxicity. Furthermore, preliminary combination studies of napabucasin with doxorubicin showed significant synergism both in vitro and in vivo. Thus, our studies provide evidence that napabucasin alone or in combination is a promising therapeutic candidate for DLBCL patients.
    [Abstract] [Full Text] [Related] [New Search]