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ß-catenin inhibitors ICG-001 and pyrvinium sensitize bortezomib-resistant multiple myeloma cells to bortezomib.
Wu, Cuicui.
Afiliação
  • Wu C; Department of Hematology, Yueyang Second People's Hospital, Yueyang, Hunan 414000, P.R. China.
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.
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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

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