In several cancers, patients with COX-2 overexpression have a poor prognosis [10-14]. Mice were irradiated only once, and celecoxib was administered orally. Mice were irradiated with 4-MV photons once the tumor volume of the control group reached 500 mm3. All mice were sacrificed when the mean tumor volume of control animals grew to 4000 mm3. The left lobes of the lungs were extracted for the measurement of metastatic nodules. == Results == Irradiation resulted in a dose-dependent increase in PGE2 production. PGE2 synthesis decreased markedly after treatment with celecoxib alone or in combination with irradiation. Compared to mice treated with low dose celecoxib, mean tumor volume decreased significantly in mice treated with a high dose of celecoxib with or without irradiation. Mice treated with a high dose celecoxib alone, with irradiation alone, or with irradiation plus celecoxib had markedly fewer metastatic lung nodules than controls. The mean metastatic area was the smallest for mice treated with irradiation plus a high dose celecoxib. == Conclusion == Oral administration of high dose celecoxib significantly inhibited tumor growth, as compared to a low dose treatment. Radiotherapy in combination with high dose celecoxib delayed tumor growth and reduced the number IKK-IN-1 of pulmonary metastases to a greater extent than celecoxib or radiotherapy alone. == Background == Radiotherapy is usually a common treatment for localized cancers. The radiation dose is important for tumor control. However, the therapeutic efficacy of radiotherapy is usually often limited by normal tissue damage within or nearby the field of radiation. In clinical practice, the radiation dose is optimized according to the probability of tumor control compared to the risks of complications due to the effects on normal tissue [1,2]. Combining chemotherapeutic brokers concurrently with radiotherapy has improved tumor control and survival. However, this combined approach also increases systemic and local toxicities during radiotherapy. Because of the increased toxicity, the overall treatment duration of radiotherapy, in addition IKK-IN-1 to chemotherapy, is usually prolonged when compared to the treatment time of radiotherapy alone [3,4]. This increased duration may decrease its efficacy for tumor control within the radiation field. To further improve tumor response and reduce normal tissue toxicity from radiotherapy or chemoradiotherapy, many novel approaches have investigated several brokers in preclinical and clinical settings. These approaches include those that selectively interfere with certain molecular processes and signaling pathways that regulate proliferation, survival, and function of normal cells. Because these brokers are preferentially associated with specific sites of the cancer cells, their targeting is usually predicted to improve the tumor response to radiotherapy or chemoradiotherapy without additional toxicity to normal tissue. Among these brokers, inhibition of cyclooxygenase (COX)-2 has been investigated as a potentially useful agent for the treatment of cancer. COX-2 is normally present in cells and tissues of the brain and kidneys, but is usually induced in pathological says such as inflammation and tumors. COX-2 promotes carcinogenesis, tumor proliferation, angiogenesis, prevention of apoptosis, and immunosuppression [5]. COX-2 overexpression has been associated with tumor behavior and prognosis in several cancers [6]. Selective inhibition COG5 of COX-2 activity in several animal models has been associated with the decrease of new blood vessel production in tumors, a decrease in new vessel formation and an increase in tumor cell apoptosis. The selective inhibition of COX-2 activity has been associated with IKK-IN-1 enhanced radiation sensitivity of tumors without enhancing the effects of radiation on normal tissue [7-9]. In this study, we evaluated the effect IKK-IN-1 of a selective COX-2 inhibitor as a radiation sensitizer in order to inhibit tumor growth and pulmonary metastasis in a Lewis Lung Carcinoma (LLC) animal model. == Methods == == Animals and.