title: Cyclo-oxygenase 2 modulates chemoresistance in breast cancer cells involving NF-kappaB.
abstract: BACKGROUND
  Breast cancer cells can develop chemoresistance after prolonged exposure to cytotoxic drugs due to expression of the multi drug resistance (MDR) 1 gene. Type 2 cyclo-oxygenase (COX-2) inhibitors reverse the chemoresistance phenotype of a medullary thyroid carcinoma cell line, TT, and of a breast cancer cell line, MCF7, by inhibiting MDR1 expression and P-gp function.
  
  
  OBJECTIVE
  investigate the role of prostaglandin (PG) in modulating chemoresistance in MCF7 cells and to explore the involved intracellular mechanisms.
  
  
  METHODS
  native and chemoresistant MCF7 cells were treated with PGH2 and resistance to Doxorubicin was tested in the presence or absence of COX-2 inhibitors.
  
  
  RESULTS
  PGH2 restores resistance to the cytotoxic effects of Doxo, with concomitant nuclear translocation of the transcription factor NF-kappaB.
  
  
  CONCLUSIONS
  COX-2 inhibitors prevent chemoresistance development in breast cancer cells by inhibiting P-gp expression and function by a mechanism that involves PGH2 generation and NF-kappaB activation.
authors: Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Ferrara, Italy.
authors: Maria Chiara
authors: MC
authors: Zatelli
authors: Daniela
authors: D
authors: Molè
authors: Federico
authors: F
authors: Tagliati
authors: Mariella
authors: M
authors: Minoia
authors: Maria Rosaria
authors: MR
authors: Ambrosio
authors: Ettore
authors: E
authors: degli Uberti
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism*; D009578:Nitrobenzenes; D044262:Prostaglandin H2 / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D013449:Sulfonamides; D014162:Transfection
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D052246:Cyclooxygenase 2 Inhibitors; D016328:NF-kappa B; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D044262:Prostaglandin H2; D004317:Doxorubicin; D008156:Luciferases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human