title: Celecoxib radiosensitizes the human cervical cancer HeLa cell line via a mechanism dependent on reduced cyclo-oxygenase-2 and vascular endothelial growth factor C expression.
abstract: OBJECTIVE
  The effects of celecoxib, a selective cyclo-oxygenase-2 (COX-2) inhibitor, on HeLa cervical cancer cell growth and radiosensitivity were investigated.
  
  
  METHODS
  Cytotoxicity was quantified using a 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium assay and effects on radiosensitivity  were assessed using the lethal dose, quasithreshold dose, fraction surviving after 2 Gy irradiation and the radiosensitization ratio (SER, based on average lethal dose) determined using a single-hit multitarget model.
  
  
  RESULTS
  Celecoxib inhibited HeLa cell proliferation in a concentration-  and time-dependent manner, with a half-maximal inhibitory concentration at 72 h of 44 μmol/l. Treatment with 20 μmol/l celecoxib for 72 h before irradiation was associated with an SER of 2.01. The SER of irradiated cells was 2.41 when treated with 40 μmol/l celecoxib before irradiation,  1.89 when treated simultaneously and 1.44 when treated after irradiation. Celecoxib downregulated COX-2 and vascular endothelial growth factor C (VEGF-C) expression evaluated immunohistochemically.
  
  
  CONCLUSIONS
  Celecoxib pretreatment radiosensitizes HeLa cells via a mechanism dependent on down-regulation  of COX-2 and VEGF-C.
authors.affiliation: Department of Obstetrics and Gynaecology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
authors.forename: A H
authors.initials: AH
authors.lastname: Wang
authors.forename: X Y
authors.initials: XY
authors.lastname: Tian
authors.forename: J J
authors.initials: JJ
authors.lastname: Yu
authors.forename: J Q
authors.initials: JQ
authors.lastname: Mi
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.forename: R F
authors.initials: RF
authors.lastname: Wang
mesh_terms: D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D011720:Pyrazoles / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects* / Q000528:radiation effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000473:pathology; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*; D014965:X-Rays
chemical_list: D011720:Pyrazoles; D011838:Radiation-Sensitizing Agents; D013449:Sulfonamides; C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib