title: Celecoxib enhances the radiosensitivity of HCT116 cells in a COX-2 independent manner by up-regulating BCCIP.
abstract: It has been reported that celecoxib, a cyclooxygenase-2 (COX-2)-selective nonsteroidal anti-inflammatory drug (NSAID), regulates the radiosensitivity of several cancer cells. BCCIP (BRCA2 and CDKN1A interacting protein) plays a critical role in maintaining the critical functions of p53 in tumor suppression and response to therapy. However, whether the effect of celecoxib on the radiosensitivity of colorectal cancer (CRC) cells is dependent on BCCIP is largely unclear. In this study, we found that celecoxib enhanced the radiosensitivity of HeLa (a human cervical carcinoma cell line), A549 (a human lung carcinoma cell line), and HCT116 cells (a human CRC cells line). Among these cells, COX-2 expression was undetected in HCT116 cells. Treatment with celecoxib significantly increased BCCIP expression in COX-2 negative HCT116 cells. Knockdown of BCCIP obviously abrogated the enhanced radiosensitivity of HCT116 cells induced by celecoxib. A combination of celecoxib and irradiation treatment induced much more γ-H2AX foci formation, higher levels of radiation injury-related proteins phosphorylation, G2/M arrest, apoptosis, and p53 and p21 expression, and lower levels of Cyclin B1 in HCT116 cells than those in cells treated with irradiation alone. However, these changes were undetected in BCCIP-silenced HCT116 cells. Therefore, these data suggest that BCCIP gene may be a radiosensitivity-related gene in CRC. Celecoxib affects the functions of p53 and inhibits the recovery from the irradiation-induced injury by up-regulating the expression of BCCIP, and subsequently regulates the expressions of genes such as p21 and Cyclin B1 to enhance the radiosensitivity of HCT116 cells in a COX-2 independent manner.
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Soochow University Suzhou 215006, People's Republic of China.
authors.forename: Xiao-Ting
authors.initials: XT
authors.lastname: Xu
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow UniversitySuzhou 215123, People's Republic of China; School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow UniversitySuzhou 215123, People's Republic of China.
authors.forename: Wen-Tao
authors.initials: WT
authors.lastname: Hu
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Soochow University Suzhou 215006, People's Republic of China.
authors.forename: Ju-Ying
authors.initials: JY
authors.lastname: Zhou
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow UniversitySuzhou 215123, People's Republic of China; School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow UniversitySuzhou 215123, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tu
keywords: BCCIP; COX-2; Celecoxib; colorectal cancer cells; radiosensitivity