[Regulation of P-glycoprotein gene expression by PKC/NF-κB-PXR signaling pathway].
Yao Xue Xue Bao
; 52(1): 51-7, 2017 Jan.
Article
en Zh
| MEDLINE
| ID: mdl-29911380
ABSTRACT
P-glycoprotein (P-gp), an ATP binding cassette protein, plays a major role in efflux transport of drugs and xenobiotics due to its abundant expression on several barriers. This study aimed to investigate the potential role of PKC/NF-κB-PXR signaling pathway in modulation of P-gp gene expression in human colon adenocarcinoma LS174T. The effect of PMA on MDR1 luciferase activity was investigated by PXR-MDR1 dual luciferase reporter gene assay. Real-time qPCR assay and Western blot analysis were used to study the gene expression of P-gp and NF-κB, respectively. Compared to the vehicle-treated group, PMA statistically decreased P-gp luciferase activity, mRNA expression and protein expression. Moreover, PMA treatment yielded a significant and dose-dependent increase in RelA/p65 translocation to nucleus. Meanwhile, a remarkable increase of the pho-IκBα status was observed in LS174T cells after treatment with PMA (1-100 nmol·L(-1)). In addition, knockdown of PKCα, NF-κB or PXR can significantly attenuate PMA-induced P-gp suppression. These results suggested that PKC/NF-κB-PXR signaling pathway might play crucial roles in modulation of P-gp gene expression.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP
/
Proteína Quinasa C-alfa
/
Factor de Transcripción ReIA
/
Receptor de la Señal 1 de Direccionamiento al Peroxisoma
Límite:
Humans
Idioma:
Zh
Revista:
Yao Xue Xue Bao
Año:
2017
Tipo del documento:
Article