Radiation is able to inhibit
tumor growth, promote
tumor cell apoptosis and prolong patient survival. However, radiation resistance remains a major impediment to
radiotherapy. Local and metastatic recurrences following radiation are still large impediments to overall survival. Although
cyclooxygenase-2 (COX-2) inhibitors may induce radiation sensitivity in
cancer cells, the underlying mechanisms are not fully understood. The present study demonstrated high potential for cell proliferation, migration and invasion in radiation-resistant
lung cancer cell lines. The present study observed the overexpression of specificity
protein 1 (Sp1) in these cells, and the overexpression of Sp1 induced upregulation of
matrix metalloproteinase (MMP)-2, MMP-9, B cell lymphoma-2, in addition to a high potential for radiation resistance, migration and invasion in these cells. The present study revealed that the COX-2 selective inhibitor,
celecoxib, enhanced radiation sensitivity and inhibited migration and invasion in these cells by inhibiting the expression and
DNA-binding activity of Sp1. Furthermore,
celecoxib downregulated Sp1 by inhibiting
c-Jun N-terminal kinase (JNK). Taken together, the present study demonstrated that Sp1 overexpression in radiation-resistant
cancer cells and
COX-2 inhibitors enhanced radiation sensitivity and inhibited the migration and invasion of
cancer cells, at least partially, via inactivation of the JNK/Sp1 signaling pathway and a decrease in Sp1
DNA-binding activity.