title: Resveratrol reverses P-glycoprotein-mediated multidrug resistance of U2OS/ADR cells by suppressing the activation of the NF-κB and p38 MAPK signaling pathways.
abstract: The present study aimed to investigate the reversal effect of resveratrol on the phenomenon of multidrug resistance in U2OS/adriamycin (ADR) cells and to clarify the molecular mechanisms. To examine the cell survival and half-inhibitory concentration (IC50) of ADR in U2OS and U2OS/ADR cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used. The accumulation of ADR in U2OS and U2OS/ADR cells was investigated by flow cytometry. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to detect the expression of multidrug resistance protein 1 (MDR1), P-glycoprotein (P-gp), p65 and p38. Compared with U2OS cells, the IC50value of ADR was significantly increased in U2OS/ADR cells, which exhibited high levels of MDR1/P-gp. However, resveratrol could drastically reduce the IC50value of ADR and the expression of MDR1/P-gp, and increased the accumulation of ADR in U2OS/ADR cells. In addition, the expression levels of p38 (phosphorylated) and p65 (acetylated and total) in U2OS/ADR cells were also significantly suppressed by resveratrol. These results suggested that the nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK) signaling pathways are correlated with ADR-induced drug resistance in U2OS/ADR cells. Furthermore, resveratrol could downregulate the expression of MDR1/P-gp and reverse the drug resistance phenomenon in U2OS/ADR cells partly at least by suppressing the activation of the NF-κB and p38 MAPK signaling pathways.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Xiliang
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Shouyu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Decheng
authors.initials: D
authors.lastname: Lv
keywords: P-glycoprotein; multidrug resistance; natural product; resveratrol; transporter