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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
Author(s) -
Yang HuiYing,
Zhao Li,
Yang Zhen,
Zhao Qing,
Qiang Lei,
Ha Jun,
Li ZhiYu,
You QiDong,
Guo QingLong
Publication year - 2012
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20789
Subject(s) - biology , downregulation and upregulation , signal transduction , pharmacology , nf κb , microbiology and biotechnology , biochemistry , gene
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. Mol. Carcinog. © 2011 Wiley Periodicals, Inc.