Oncostatin M reverses ABCG2-mediated mitoxantrone resistance

Mitoxantrone resistant variant of SW620 line was developed, characterized and subsequently used as a model system to determine oncostatin M ability to modulate MDR phenomenon. The selection regimen allowed for overexpression of ABCG2 and ABCB1 both at the RNA and protein level, which was further con...

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Veröffentlicht in:Biomedicine & pharmacotherapy 2024-07, Vol.176, p.116861, Article 116861
Hauptverfasser: Błauż, Andrzej, Wachulec, Marcin, Rychlik, Błażej
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Sprache:eng
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Zusammenfassung:Mitoxantrone resistant variant of SW620 line was developed, characterized and subsequently used as a model system to determine oncostatin M ability to modulate MDR phenomenon. The selection regimen allowed for overexpression of ABCG2 and ABCB1 both at the RNA and protein level, which was further confirmed by functional assays. Oncostatin M supplementation resulted in partial reversal of MDR phenotype by decreasing overexpression of ABCG2 demonstrating for the first time the ability of this cytokine for selective down-regulation of one of MDR proteins. •New MDR clone of SW620 was obtained by mitoxantrone selection.•SW620Mito variant significantly overexpressed ABCG2 transporter.•Oncostatin M was used as a novel approach to overcome MDR phenotype. This cytokine decreased overexpression of ABCG2.•Oncostatin M mitigate resistance toward series of ABCG2 substrates (like mitxantrone, elacridar, lisitnib, etc.).•Fluorescent dyes transport assays were performed revealing decreased transport capabilities mediated by ABCG2.
ISSN:0753-3322
1950-6007
1950-6007
DOI:10.1016/j.biopha.2024.116861