title: Modulation of ionizing radiation-induced G2 arrest by cyclooxygenase-2 and its inhibitor celecoxib.
abstract: OBJECTIVE
  Prolongation or attenuation of ionizing radiation (IR)-induced G(2)-M arrest in cyclooxygenase-2 (COX-2) overexpressing or celecoxib-treated cells, respectively, has been previously observed. To better understand the molecular mechanisms involved, we investigated the molecules involved in G(2) checkpoint pathways after treatment with IR +/- celecoxib.
  
  
  METHODS
  Various molecules in the G(2) checkpoint pathways were investigated in HCT-116-Mock and -COX-2 cells. Western blot, reverse transcriptase polymerase chain reaction, confocal microscopy, and fluorescence activated cell sorter (FACS) analyses were performed to investigate whether expression and activity of the ataxia telangiectasia and rad3-related (ATR) could be modulated by COX-2 and its selective inhibitors.
  
  
  RESULTS
  COX-2 overexpression increased expression and activity of ATR after IR exposure. Celecoxib downregulated ATR in all tested cell lines independent of COX-2 expression, but downregulation was greater in COX-2 overexpressing cells after cells were irradiated. Celecoxib pretreatment before radiation caused strongly inhibited G(2) arrest.
  
  
  CONCLUSIONS
  COX-2 appears to prolong IR-induced G(2) arrest by upregulating ATR. Celecoxib downregulated ATR preferentially in irradiated COX-2 overexpressing cells. Celecoxib may radiosensitize cancer cells by inhibiting G(2) arrest through ATR downregulation.
authors.affiliation: Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Jun
authors.forename: Young Mee
authors.initials: YM
authors.lastname: Kim
authors.forename: Soo Yeon
authors.initials: SY
authors.lastname: Park
authors.forename: Ji Sun
authors.initials: JS
authors.lastname: Park
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Lee
authors.forename: Shin Ae
authors.initials: SA
authors.lastname: Choi
authors.forename: Hongryull
authors.initials: H
authors.lastname: Pyo
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D000068579:Celecoxib; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004260:DNA Repair / Q000187:drug effects; D015536:Down-Regulation; D005434:Flow Cytometry / Q000379:methods; D016195:G2 Phase / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D045325:HCT116 Cells; D006801:Humans; D008938:Mitosis / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D018797:Cell Cycle Proteins; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D000068579:Celecoxib