title: Astragaloside Ⅳ reduces the expression level of P-glycoprotein in multidrug-resistant human hepatic cancer cell lines.
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.
authors.affiliation: Department of Pharmacy, Yijishan Affiliated Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China.
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Du-Juan
authors.initials: DJ
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, Anqing Shili Hospital, Anqing, Anhui 246003, P.R. China.
authors.forename: Can
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, Yijishan Affiliated Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Yijishan Affiliated Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China.
authors.forename: Wen-Ke
authors.initials: WK
authors.lastname: Xu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000633:toxicity; D001692:Biological Transport; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000633:toxicity; D005472:Fluorouracil / Q000378:metabolism / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics; D020112:Rhodamine 123 / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology* / Q000633:toxicity; D014315:Triterpenes / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D012503:Saponins; D014315:Triterpenes; D020112:Rhodamine 123; C052064:astragaloside A; D005472:Fluorouracil