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Regulation of P-glycoprotein gene expression by PKC/NF-κB-PXR signaling pathway
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Yu-hua LI1, 2, Ling HUANG3, Xiao-hua WEI1, Jin-hua WEN1, Guo-ping ZHONG2, Min HUANG2, Hui-chang BI2, *
Acta Pharmaceutica Sinica | 2017, 52(1) : 51 - 57
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Acta Pharmaceutica Sinica | 2017, 52(1): 51-57
• SPECIAL REPORTS •
Regulation of P-glycoprotein gene expression by PKC/NF-κB-PXR signaling pathway
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Yu-hua LI1, 2, Ling HUANG3, Xiao-hua WEI1, Jin-hua WEN1, Guo-ping ZHONG2, Min HUANG2, Hui-chang BI2, *
Affiliations
  • 1. The First Affiliated Hospital of Nanchang University, Nanchang 330006, China
  • 2. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
  • 3. School of Pharmaceutical Sciences, Hainan Medical University, Haikou 571199, China
Published: 2017-01-12 doi: 10.16438/j.0513-4870.2016-1003
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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.

protein kinase C  /  nuclear factor κB  /  pregnane X receptor  /  p-glycoprotein  /  gene expression
Yu-hua LI, Ling HUANG, Xiao-hua WEI, Jin-hua WEN, Guo-ping ZHONG, Min HUANG, Hui-chang BI. Regulation of P-glycoprotein gene expression by PKC/NF-κB-PXR signaling pathway[J]. Acta Pharmaceutica Sinica, 2017 , 52 (1) : 51 -57 . DOI: 10.16438/j.0513-4870.2016-1003
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Article Info
doi: 10.16438/j.0513-4870.2016-1003
  • Receive Date：2016-10-17
  • Online Date：2026-01-14
  • Published：2017-01-12
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History
  • Received：2016-10-17
  • Revised：2016-11-22
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Affiliations
    1. The First Affiliated Hospital of Nanchang University, Nanchang 330006, China
    2. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
    3. School of Pharmaceutical Sciences, Hainan Medical University, Haikou 571199, China
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多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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