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Regulation of P-glycoprotein gene expression by PKC/NF-κB-PXR signaling pathway / 药学学报
Acta Pharmaceutica Sinica ; (12): 51-57, 2017.
Article in Chinese | WPRIM | ID: wpr-779819
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.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Acta Pharmaceutica Sinica Year: 2017 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Acta Pharmaceutica Sinica Year: 2017 Type: Article