Repurposing Penfluridol in Combination with Temozolomide for the Treatment of Glioblastoma.
glioblastoma
penfluridol
sphere forming cell
temozolomide
tumor growth
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
05 Sep 2019
05 Sep 2019
Historique:
received:
30
07
2019
revised:
23
08
2019
accepted:
30
08
2019
entrez:
8
9
2019
pubmed:
8
9
2019
medline:
8
9
2019
Statut:
epublish
Résumé
Despite the presence of aggressive treatment strategies, glioblastoma remains intractable, warranting a novel therapeutic modality. An oral antipsychotic agent, penflurido (PFD), used for schizophrenia treatment, has shown an antitumor effect on various types of cancer cells. As glioma sphere-forming cells (GSCs) are known to mediate drug resistance in glioblastoma, and considering that antipsychotics can easily penetrate the blood-brain barrier, we investigated the antitumor effect of PFD on patient-derived GSCs. Using five GSCs, we found that PFD exerts an antiproliferative effect in a time- and dose-dependent manner. At IC50, spheroid size and second-generation spheroid formation were significantly suppressed. Stemness factors, SOX2 and OCT4, were decreased. PFD treatment reduced cancer cell migration and invasion by reducing the Integrin α6 and uPAR levels and suppression of the expression of epithelial-to-mesenchymal transition (EMT) factors, vimentin and Zeb1. GLI1 was found to be involved in PFD-induced EMT inhibition. Furthermore, combinatorial treatment of PFD with temozolomide (TMZ) significantly suppressed tumor growth and prolonged survival in vivo. Immunostaining revealed decreased expression of GLI1, SOX2, and vimentin in the PFD treatment group but not in the TMZ-only treatment group. Therefore, PFD can be effectively repurposed for the treatment of glioblastoma by combining it with TMZ.
Identifiants
pubmed: 31492002
pii: cancers11091310
doi: 10.3390/cancers11091310
pmc: PMC6770574
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : National Research Foundation Korea
ID : 2014R1A2A2A01005274
Organisme : National Research Foundation Korea
ID : 2017R1D1A1B03034199
Déclaration de conflit d'intérêts
All authors declare no financial conflict of interest.
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