title: Celecoxib increases miR-222 while deterring aromatase-expressing breast tumor growth in mice.
abstract: BACKGROUND
  Breast cancer is one of the most deadly diseases in women. Inhibiting the synthesis of estrogen is effective in treating patients with estrogen-responsive breast cancer. Previous studies have demonstrated that use of cyclooxygenase (COX) inhibitors is associated with reduced breast cancer risk.
  
  
  METHODS
  In the present study, we employed an established mouse model for postmenopausal breast cancer to evaluate the potential mechanisms of the COX-2 inhibitor celecoxib. Aromatase-expressing MCF-7 cells were transplanted into ovariectomized athymic mice. The animals were given celecoxib at 1500 ppm or aspirin at 200 ppm by oral administration with androstenedione injection.
  
  
  RESULTS
  Our results showed that both COX inhibitors could suppress the cancer xenograft growth without changing the plasma estrogen level. Protein expression of ERα, COX-2, Cyclin A, and Bcl-xL were reduced in celecoxib-treated tumor samples, whereas only Bcl-xL expression was suppressed in those treated with aspirin. Among the breast cancer-related miRNAs, miR-222 expression was elevated in samples treated with celecoxib. Further studies in culture cells verified that the increase in miR-222 expression might contribute to ERα downregulation but not the growth deterrence of cells.
  
  
  CONCLUSIONS
  Overall, this study suggested that both celecoxib and aspirin could prevent breast cancer growth by regulating proteins in the cell cycle and apoptosis without blocking estrogen synthesis. Besides, celecoxib might affect miR expression in an undesirable fashion.
authors.forename: Tsz Yan
authors.initials: TY
authors.lastname: Wong
authors.forename: Fengjuan
authors.initials: F
authors.lastname: Li
authors.forename: Shu-mei
authors.initials: SM
authors.lastname: Lin
authors.forename: Franky L
authors.initials: FL
authors.lastname: Chan
authors.forename: Shiuan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Rm,507C MMW Bldg, Shatin, Hong Kong. laikleung@cuhk.edu.hk.
authors.forename: Lai K
authors.initials: LK
authors.lastname: Leung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000068579:Celecoxib; D002453:Cell Cycle / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D050703:E2F2 Transcription Factor / Q000235:genetics; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D061986:MCF-7 Cells; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D011720:Pyrazoles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D001141:Aromatase; D001241:Aspirin; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D050703:E2F2 Transcription Factor; D004958:Estradiol; D047628:Estrogen Receptor alpha; D035683:MicroRNAs; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; C525710:MIR222, human