title: Parecoxib: an enhancer of radiation therapy for colorectal cancer.
abstract: BACKGROUND
  To study the effect of parecoxib, a novel cyclooxygenase-2 selective inhibitor, on the radiation response of colorectal cancer (CRC) cells and its underlying mechanisms.
  
  
  METHODS
  Both in vitro colony formation and apoptosis assays as well as in vivo mouse xenograft experiments were used to explore the radiosensitizing effects of parecoxib in human HCT116 and HT29 CRC cells.
  
  
  RESULTS
  Parecoxib sensitized CRC cells to radiation in vitro with a sensitivity enhancement ratio of 1.32 for HCT116 cells and 1.15 for HT29 cells at a surviving fraction of 0.37. This effect was partially attributable to enhanced apoptosis induction by parecoxib combined with radiation, as illustrated using an in vitro apoptosis assays. Parecoxib augmented the tumor response of HCT116 xenografts to radiation, achieving growth delay more than 20 days and an enhancement factor of 1.53. In accordance with the in vitro results, parecoxib combined with radiation resulted in less proliferation and more apoptosis in tumors than radiation alone. Radiation monotherapy decreased microvessel density (MVD) and microvessel intensity (MVI), but increased the hypoxia level in xenografts. Parecoxib did not affect MVD, but it increased MVI and attenuated hypoxia.
  
  
  CONCLUSIONS
  Parecoxib can effectively enhance radiation sensitivity in CRC cells through direct effects on tumor cells and indirect effects on tumor vasculature.
authors: Department of Radiation Oncology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, China E-mail : kmtjing@163.com.
authors: Wei
authors: W
authors: Xiong
authors: Wen-Hui
authors: WH
authors: Li
authors: Yong-Xin
authors: YX
authors: Jiang
authors: Shan
authors: S
authors: Liu
authors: Yi-Qin
authors: YQ
authors: Ai
authors: Rong
authors: R
authors: Liu
authors: Li
authors: L
authors: Chang
authors: Ming
authors: M
authors: Zhang
authors: Xiao-Li
authors: XL
authors: Wang
authors: Han
authors: H
authors: Bai
authors: Hong
authors: H
authors: Wang
authors: Rui
authors: R
authors: Zheng
authors: Jing
authors: J
authors: Tan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects* / Q000528:radiation effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D007124:Immunoenzyme Techniques; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014965:X-Rays; D023041:Xenograft Model Antitumor Assays
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D007555:Isoxazoles; D011838:Radiation-Sensitizing Agents; C409945:parecoxib