Background: To study the effect of parecoxib, a novel cyclooxygenase-2 selective inhibitor, on the radiationresponse of colorectal cancer (CRC) cells and its underlying mechanisms. Materials and
Methods: Both in vitrocolony formation and apoptosis assays as well as in vivo mouse xenograft experiments were used to explore theradiosensitizing effects of parecoxib in human HCT116 and HT29 CRC cells.
Results: Parecoxib sensitized CRCcells to radiation in vitro with a sensitivity enhancement ratio of 1.32 for HCT116 cells and 1.15 for HT29 cells ata surviving fraction of 0.37. This effect was partially attributable to enhanced apoptosis induction by parecoxibcombined with radiation, as illustrated using an in vitro apoptosis assays. Parecoxib augmented the tumor responseof HCT116 xenografts to radiation, achieving growth delay more than 20 days and an enhancement factor of1.53. In accordance with the in vitro results, parecoxib combined with radiation resulted in less proliferationand 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 affectMVD, but it increased MVI and attenuated hypoxia.
Conclusions: Parecoxib can effectively enhance radiationsensitivity in CRC cells through direct effects on tumor cells and indirect effects on tumor vasculature.