Systematic analyses of genes associated with radio sensitizing effect by celecoxib, a specific cyclooxygenase-2 inhibitor

To investigate genes regulated by COX-2 or a COX-2 specific inhibitor, celecoxib, in irradiated cancer cells, we analyzed changes in gene expression using complementary DNA microarray following celecoxib or combined celecoxib and ionizing radiation (IR) treatment in a stable COX-2 knockdown A549 (AS) and a mock cell line (AN). Thirty-six genes were differentially expressed by COX-2 knockdown. Celecoxib changed the expressions of 40 and 69 genes in AN and AS cells, respectively. Twenty-seven genes were synchronously regulated by COX-2 and celecoxib. Among these, celecoxib regulated ras homolog gene family B and mitosin protein expression in a COX-2 dependent manner, especially in irradiated cells. In addition, we identified 11 genes that changed by more than 1. 5 times the expected additive values after celecoxib and IR treatment. The current study may provide evidence that COX-2 or celecoxib regulates various intracellular functions in addition to their enzymatic activity regulation. We also identified candidate molecules that may be responsible for COX-2-dependent radiosensitization by celecoxib.