ArticleFrontiers in oncology2026
Umbralisib antagonizes multidrug resistance in ABCB1-overexpressing cancer cells.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: ABCB1-mediated multidrug resistance (MDR) reduces the intracellular accumulation of anticancer drugs and limits chemotherapy efficacy. This study investigated whether umbralisib, a dual PI3Kδ/CK1ϵ inhibitor, could reverse ABCB1-mediated MDR. Methods: The reversal effect of umbralisib was evaluated in ABCB1-overexpressing drug-selected and transfected cell models using MTT assays. Drug accumulation and efflux assays, ATPase analysis, molecular docking, Western blotting, immunofluorescence, apoptosis analysis, and 3D spheroid assays were performed to explore the underlying mechanism. Results: Umbralisib significantly sensitized ABCB1-overexpressing cells to paclitaxel, vincristine, and doxorubicin in a concentration-dependent manner, but did not markedly reverse ABCC1-, ABCG2-, or ABCC10-mediated MDR. Mechanistically, umbralisib increased intracellular [ Conclusion: Umbralisib reverses ABCB1-mediated MDR mainly by inhibiting ABCB1 drug efflux rather than altering transporter expression or localization, providing mechanistic insight into the modulation of ABCB1-mediated chemoresistance.
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