Astragaloside Ⅳ reduces the expression level of P‑glycoprotein in multidrug‑resistant human hepatic cancer cell lines

Wang,Pei‑Pei; Xu,Du‑Juan; Huang,Can; Wang,Wei‑Ping; Xu,Wen‑Ke

doi:10.3892/mmr.2014.2074

Astragaloside Ⅳ reduces the expression level of P‑glycoprotein in multidrug‑resistant human hepatic cancer cell lines

Authors:
- Pei‑Pei Wang
- Du‑Juan Xu
- Can Huang
- Wei‑Ping Wang
- Wen‑Ke Xu
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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, Department of Pharmacy, Anqing Shili Hospital, Anqing, Anhui 246003, P.R. China
Published online on: March 27, 2014 https://doi.org/10.3892/mmr.2014.2074
Pages: 2131-2137
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Astragaloside is a saponin widely used in traditional Chinese medicine and has been reported to be a potent multidrug resistance (MDR) reversal agent. The present study investigated the role of astragaloside Ⅳ (ASIV) in the regulation of P‑glycoprotein (P‑gp, encoded by the mdr1 gene) and its effect on the reversal of MDR. The activity of ASIV was evaluated using human hepatic cancer cells Bel‑7402 and the corresponding 5‑fluorouracil (5‑FU) resistant cells Bel‑7402/FU. ASIV (0.08 mg/ml) potentiated the cytotoxicity of 5‑FU which was demonstrated using the MTT assay on Bel‑7402/FU cells. ASIV reduced the expression of P‑gp as was revealed by immunocytochemistry. Accumulation and efflux studies with the P‑gp substrate, rhodamine 123 (Rh123), demonstrated that ASIV inhibited P‑gp‑mediated drug efflux. Furthermore, it was demonstrated that ASⅣ enhanced the drug accumulation of 5‑FU using a high performance liquid chromatography (HPLC) assay for drug resistant cells. Furthermore, ASIV may downregulate the expression of P‑gp, which was examined using western blot analysis and polymerase chain reaction. In conclusion, the results of the present study indicated that ASIV reverses the drug resistance of Bel‑7402/FU cells by downregulating the expression of mdr1. ASIV may represent a potent modulator of P‑gp‑mediated MDR in hepatic cancer therapy.

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