title: Reversal effects of droloxifene on multidrug resistance in adriamycin-resistant K562 cell line.
abstract: OBJECTIVE
  To study the reversal effects of droloxifene (DRO) on multidrug resistance (MDR) in K562 cell line resistant to adriamycin (ADR).
  
  
  METHODS
  K562 cell line resistant to ADR (K562/A02) and K562 cell line sensitive to ADR (K562) were treated with DRO. Using MTT assay, chemosensitivity to ADR in DRO-treated K562 cell lines was studied. Before and after the treatment with DRO 10 micromol/L, MDR1 and GSTpi gene expression were assayed by reverse transcription-polymerase chain reaction and immunocytochemistry assay. Flow cytometry was used to determine intracellular ADR concentration.
  
  
  RESULTS
  DRO significantly reversed MDR in K562/A02 (P < 0.01). After treatment of DRO 20, 10, and 5 micromol/L, the chemosensitivity to ADR was increased to 14, 13, and 4 folds, respectively. The reversal activity of DRO was similar to that of verapamil (VRP). After treated with DRO 10 micromol/L, both MDR1 and GSTpi mRNA expression began to decline on the 2nd day, and significantly decreased on the 5th day (P<0.01). The changes in P-gp and GSTpi protein expression were similar to that of their mRNA expression. Two hours after treatment of DRO 20, 10, and 5 micromol/L, intracellular ADR concentration in K562/A02 was increased to 2.9, 2.3, and 1.5 folds, respectively. However, DRO did not markedly increase ADR accumulation in K562.
  
  
  CONCLUSIONS
  DRO had strong reversal effect on MDR in K562/A02, which was comparable to that of VRP, but the reversal effect was via different pathways.
authors.affiliation: Department of Oncology, Cancer Center, Xin Hua Hospital, Shanghai Second Medical University, Shanghai 200092, China. Ljee@citiz.net
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: L Z
authors.initials: LZ
authors.lastname: Xu
authors.forename: J J
authors.initials: JJ
authors.lastname: Yao
authors.forename: W J
authors.initials: WJ
authors.lastname: Guo
authors.forename: P
authors.initials: P
authors.lastname: Xia
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology*; D004347:Drug Interactions; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020014:K562 Cells / Q000187:drug effects*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D000975:Antioxidants; D013629:Tamoxifen; C038345:droloxifene; D004317:Doxorubicin