title: Potential role of cyclooxygenase-2 on the regulation of the drug efflux transporter ABCG2 in breast cancer cell lines.
abstract: OBJECTIVE
  ABCG2 (BCRP) implicated as a member of the multidrug resistance (MDR) proteins in tumors, mediating efflux of a wide spectrum of anticancer drugs. In recent years, there has been an increasing tendency toward the exploring of the potential link between cyclooxygenase-2 (COX-2) expression and development of multidrug resistance phenotype in patients with cancer. The aim of this study was to investigate the role of the COX-2 in modulating drug efflux by ABCG2 in a group of breast cancer cell lines.
  
  
  METHODS
  The cytotoxicity of COX-2 inducer (TPA, tetradecanoyl phorbol acetate) and its inhibitor (celecoxib) was determined by an MTT assay. ABCG2 activity was measured by flow cytometric mitoxantrone efflux assay.
  
  
  RESULTS
  TPA exhibited very little inhibitory activity in all cell lines, while long-term treatment with celecoxib significantly inhibited the growth of all cell lines. Furthermore, using mitoxantrone efflux assay was shown that TPA could increase ABCG2 activity in all the cell lines with the greatest stimulatory effects in MCF7-MX (more than 6 times the control level). It seemed that celecoxib inverted the effects of TPA on ABCG2 activity. This was more obvious in MCF7-MX.
  
  
  CONCLUSIONS
  The results suggest a probable causal link between COX-2 and ABCG2 activity. The use of celecoxib for adjuvant therapy in cancer treatment may contribute to decreased resistance to chemotherapeutic drugs transported by ABCG2.
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. kalaliniaf831@mums.ac.ir
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Kalalinia
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Elahian
authors.forename: Javad
authors.initials: J
authors.lastname: Behravan
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008942:Mitoxantrone / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D009363:Neoplasm Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D008942:Mitoxantrone; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D013755:Tetradecanoylphorbol Acetate