Oroxylin A reverses multi-drug resistance of human hepatoma BEL7402/5-FU cells via downregulation of P-glycoprotein expression by inhibiting NF-κB signaling pathway

Abstract

In this study, oroxylin A showed strong reversal potency in BEL7402/5-FU cells and the reversal fold (RF) reached 4.69. Simultaneously, rhodamine-123 accumulation assay and flow cytometry analysis demonstrated oroxylin A could increase drug accumulation. When combined with oroxylin A, 5-FU showed inducing apoptosis effect more seriously in DAPI staining experiment. Moreover, the mRNA and protein expression of multi-drug resistance gene (MDR1) were also decreased by oroxylin A. Further experiments exhibited that oroxylin A can downregulate P-gp expression through inhibiting nuclear factor-κB (NF-κB) signaling pathway, which might be the mechanism of reversal resistance of oroxylin A. In summary, oroxylin A could be a good candidate for the development of new MDR reversal agent and its reversal mechanism probably due to the suppression of P-gp expression via inhibiting NF-κB signaling pathway.