ß-catenin inhibitors ICG-001 and pyrvinium sensitize bortezomib-resistant multiple myeloma cells to bortezomib.
Oncol Lett
; 24(1): 205, 2022 Jul.
Article
em En
| MEDLINE
| ID: mdl-35720475
Although bortezomib (BTZ) displays efficacy in treating multiple myeloma (MM), BTZ resistance in MM patients has been reported. Meanwhile, treating BTZ resistant MM cells with ß-catenin inhibitors have demonstrated the ability to reserve BTZ resistance. Thus, the present study aimed to investigate the synergistic effect of the ß-catenin inhibitors, ICG-001 and pyrvinium (PP), with BTZ in the treatment of BTZ-resistant MM cells. Different concentrations of ICG-001 (0-32 µM) or PP (0-32 nM) were used to treat the BTZ-resistant RPMI-8226 (RPMI-8226BR) and BTZ-resistant KMS-11 (KMS-11BR) cell lines, followed by a BTZ combination treatment. Subsequently, cell viability and apoptosis in these two cell lines were determined by CCK-8 assay and flow cytometry, respectively. The proteins involved in the Wnt/ß-catenin signaling pathway were detected using western blotting. The Wnt/ß-catenin signaling pathway was activated in the RPMI-8226BR and the KMS-11BR cells. In addition, the cell viability of RPMI-8226BR and KMS-11BR cells were decreased following ß-catenin inhibitor (ICG-001 and PP) treatment alone. Furthermore, the ß-catenin inhibitors, ICG-001 and PP, plus BTZ combination treatment revealed a notable decrease in cell viability and a marked increase in cell apoptosis rate, compared with that in cells treated with ICG-001, PP or BTZ alone in the RPMI-8226BR and KMS-11BR cell lines. In conclusion, the ß-catenin inhibitors, ICG-001 and PP not only increased apoptosis, but also sensitized BTZ-resistant MM cells to BTZ, indicating their potential therapeutic application in MM.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Oncol Lett
Ano de publicação:
2022
Tipo de documento:
Article
País de publicação:
Grécia