Tetrandrine prevents multidrug resistance in the osteosarcoma cell line, U-2OS, by preventing Pgp overexpression through the inhibition of NF-kappaB signaling.

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Lu Y, Li F, Xu T, Sun J

Tetrandrine prevents multidrug resistance in the osteosarcoma cell line, U-2OS, by preventing Pgp overexpression through the inhibition of NF-kappaB signaling.

Int J Mol Med. 2017 Apr;39(4):993-1000. doi: 10.3892/ijmm.2017.2895. Epub 2017 Feb 17.

PubMed ID

28260091 [ View in PubMed

]

Abstract

The development of multidrug resistance (MDR) remains a major limitation to successful chemotherapy in osteosarcoma. Preventing the introduction of MDR has been a research hotspot in clinical and investigational oncology. The aim of this study was to evaluate the preventive effects of tetrandrine (TET) against MDR in osteosarcoma. For this purpose, U-2OS human osteosarcoma cells were treated with paclitaxel alone or a combination of paclitaxel with TET. The cells treated with paclitaxel alone eventually acquired MDR along with the overexpression of and highly activated P-glycoprotein (Pgp), while the cells treated with the paclitaxel-TET combination were sensitive to chemotherapeutic drugs and expressed decreased levels of Pgp and less Pgp activity. The promoter activities of MDR gene 1 (MDR1) and nuclear factor (NF)kappaB, and the expression levels of NF-kappaB and p-IkappaB-alpha were all enhanced in the cells cultured with paclitaxel alone. NF-kappaB DNA-binding activity and the binding ability of NF-kappaB to the MDR1 promoter were also enhanced in the cells cultured with paclitaxel alone compared to the control cells. However, the expression and activity of NF-kappaB were significantly decreased in the paclitaxel-TET combination-treated group as compared with the cells treated with paclitaxel alone. On the whole, our findings suggest that TET prevents paclitaxel-induced MDR by inhibiting Pgp overexpression through a mechanism that may involve the inhibition of NF-kappaB signaling in osteosarcoma.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Tetrandrine	P-glycoprotein 1	Protein	Humans	Unknown	Inhibitor	Details