title: Effect of celecoxib on inhibiting tumor repopulation during radiotherapy in human FaDu squamous cell carcinoma.
abstract: OBJECTIVE
  FaDu human squamous cell carcinoma (FaDu-hSCC) demonstrated accelerated tumor repopulation during fractionated irradiation with pathological validation in a xenograft model system. Previous studies showed that the selective cyclooxygenase (COX)-2 inhibitor celecoxib can enhance the tumor response to radiotherapy. So we aimed to explore the effect of celecoxib in inducing apoptosis and inhibiting repopulation of FaDu tumors in nude mice during fractionated radiotherapy.
  
  
  METHODS
  FaDu-hSCC was transplanted into the right hind leg of BALB/C nude mice. Mice were treated with celecoxib and/or fractionated irradiation. Celecoxib (100 mg/kg/day) was administered by daily gavage. Irradiation was delivered with 12 to 18 fractions of 3.0 Gy daily or every second day based on Petersen's repopulation model. At different time points, tumors were excised for immunohistochemistry staining.
  
  
  RESULTS
  Significant tumor repopulation occurred after about 18 days of radiotherapy. On average, Ki-67 and bromodeoxyuridine (BrdUrd) labeling indices (LI) decreased with daily irradiation (both p < 0.05) and increased with every-second-day irradiation (both p > 0.05), suggesting accelerated repopulation. Ki-67 LI decreased in celecoxib concurrent with radiotherapy for 12 fractions in 24 days and 18 fractions in 36 days compared with irradiated alone (p = 0.004 and 0.042, respectively). BrdUrd LI values were lower in the concurrent groups than irradiated alone (p = 0.001 and 0.006, respectively). Epithelial growth factor receptor (EGFR) expression score decreased in the concurrent groups than irradiated alone (p = 0.037 and 0.031, respectively). Caspase-3 expression scores were higher in the concurrent groups than irradiated alone (p = 0.05 and 0.006, respectively).
  
  
  CONCLUSIONS
  Celecoxib concurrent radiotherapy could inhibit tumor repopulation and increase tumor apoptosis during the treatment in FaDu squamous cell carcinoma.
authors.affiliation: Jinan University, Shandong Academy of Medical Sciences, Jinan, Shandong, PR China ; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, PR China ; These two authors contribute equally to this work, are co-authors.
authors.forename: Jia
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, PR China ; These two authors contribute equally to this work, are co-authors.
authors.forename: Jin-Bo
authors.initials: JB
authors.lastname: Yue
authors.affiliation: Graduate Education Centre of Shandong Academy of Medical Sciences, Jinan, Shandong, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, PR China.
authors.forename: Xin-Dong
authors.initials: XD
authors.lastname: Sun
authors.affiliation: Jinan University, Shandong Academy of Medical Sciences, Jinan, Shandong, PR China.
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Hu
authors.affiliation: Department of Pathology, Shandong Cancer Hospital and Institute, Jinan, Shandong, PR China.
authors.forename: Ju-Jie
authors.initials: JJ
authors.lastname: Sun
authors.affiliation: Department of Pathology, Shandong Cancer Hospital and Institute, Jinan, Shandong, PR China.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, PR China.
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Yu
keywords: apoptosis; cyclooxygenase (COX)-2 inhibitor; fractionated radiotherapy; tumor repopulation