Low-Dose Salinomycin Targets Multidrug Resistance via P-Glycoprotein and NF-κB in Osteosarcoma Cells

Advance Sustainable Science, Engineering and Technology (ASSET)
Universitas Persatuan Guru Republik Indonesia Semarang

📄 Abstract

Chemotherapy resistance in osteosarcoma remains a major clinical obstacle, largely driven by drug efflux mechanisms mediated by P-glycoprotein (ACBC1/ABCB1) and activation of NF-κB signaling (NFKB1). This study investigated the potential of Salinomycin to modulate these multidrug resistance–associated genes in U2OS osteosarcoma cells and explore its role in overcoming chemoresistance. A true experimental post-test-only control group design was used. U2OS cells were treated with varying concentrations of Salinomycin, doxorubicin, and their combination. Cell viability was assessed using MTT assay, while gene expression of ACBC1 and NFKB1 was quantified using qRT-PCR with SYBR Green chemistry. Relative expression levels were analyzed using the 2−ΔΔCt method normalized to GAPDH. Salinomycin demonstrated dose-dependent cytotoxic effects in the low micromolar range. At lower concentrations, it significantly reduced NFKB1 expression, while also showing a tendency to downregulate ACBC1. However, intermediate concentrations showed variable effects, including a transient increase in NFKB1 expression. The combination treatment with doxorubicin produced only modest and non-significant changes in both resistance-related genes. Overall, low-dose Salinomycin exhibited a more consistent suppressive effect on NF-κB signaling, suggesting a potential role in sensitizing osteosarcoma cells to chemotherapy. In contrast, higher doses primarily enhanced cytotoxicity without clearly improving suppression of resistance markers. This study highlights a novel dual-action, dose-dependent regulatory effect of Salinomycin at the transcriptomic level, targeting both drug efflux (ACBC1/ABCB1) and survival signaling (NF-κB/NFKB1). These findings provide new insight into its potential as an adjunct agent in overcoming multidrug resistance in osteosarcoma and warrant further validation at the protein and functional levels.

🔖 Keywords

#Multidrug resistance; NF-κB; osteosarcoma; P-Glycoprotein; salinomycin

ℹ️ Informasi Publikasi

Tanggal Publikasi
25 June 2026
Volume / Nomor / Tahun
Tahun 2026

📝 HOW TO CITE

Ayu, Onarisa; Rusda, Muhammad; Sembiring, Rosita Juwita; Nasution, Iqbal Pahlevi Adeputra; Mahyudin, Ferdiansyah; Amin, Mustafa Mahmud; Pasaribu, Hotma Partogi; Tobing, Tina Christina Lumban, "Low-Dose Salinomycin Targets Multidrug Resistance via P-Glycoprotein and NF-κB in Osteosarcoma Cells," Advance Sustainable Science, Engineering and Technology (ASSET), Jun. 2026.

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