Astragaloside IV downregulates the expression of MDR1 in Bel‑7402/FU human hepatic cancer cells by inhibiting the JNK/c‑Jun/AP‑1 signaling pathway

Wang,Pei‑Pei; Luan,Jia‑Jie; Xu,Wen‑Ke; Wang,Lin; Xu,Du‑Juan; Yang,Chun‑Yan; Zhu,Yan‑Hong; Wang,Ya‑Qin

doi:10.3892/mmr.2017.6924

Astragaloside IV downregulates the expression of MDR1 in Bel‑7402/FU human hepatic cancer cells by inhibiting the JNK/c‑Jun/AP‑1 signaling pathway

Authors:
- Pei‑Pei Wang
- Jia‑Jie Luan
- Wen‑Ke Xu
- Lin Wang
- Du‑Juan Xu
- Chun‑Yan Yang
- Yan‑Hong Zhu
- Ya‑Qin Wang
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Affiliations: Department of Pharmacy, Yijishan Affiliated Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China, Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, School of Pharmacy, Wannan Medical College, Wuhu, Anhui 241001, P.R. China
Published online on: July 5, 2017 https://doi.org/10.3892/mmr.2017.6924
Pages: 2761-2766

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Abstract

Previous studies demonstrated that astragaloside IV (ASIV) is a potential P‑glycoprotein (P‑gp)‑mediated multidrug resistance (MDR) reversal agent through mechanisms involving downregulation of the gene expression of mdr1. In order to investigate whether the c‑Jun N‑terminal kinase (JNK) signaling pathway is involved in the mechanism underlying ASIV‑induced downregulated the expression of mdr1, the present study used 5‑fluorouracil‑resistant Bel‑7402/FU human hepatic cancer cells as target cells. ASIV (0.1 mM) decreased the protein expression of phosphorylated (p)‑JNK and p‑c‑Jun in the Bel‑7402/FU cells, as determined using western blot analysis. Treatment with the JNK pathway inhibitor, SP600125, at a concentration of 11 µM, decreased the mRNA expression levels of mdr1 and P‑gp, as determined using reverse transcription‑quantitative polymerase chain reaction and western blot analyses, and similar effects were observed following exposure to ASIV. Furthermore, electrophoretic mobility shift assays demonstrated that the DNA‑binding activity of activator protein‑1 (AP‑1) was decreased by 0.1 mM ASIV or 11 µM SP600125. Flow cytometric analysis revealed that 0.1 mM ASIV or 11 µM SP600125 increased the intracellular accumulation of fluorescent P‑gp substrates, including rhodamine 123. Taken together, these results indicated that ASIV reversed the drug resistance of Bel‑7402/FU cells by downregulating the expression of mdr1 via inhibition of the JNK/c‑Jun/AP‑1 signaling pathway.

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