A COX-2 inhibitor enhances the antitumor effects of chemotherapy and radiotherapy for esophageal squamous cell carcinoma

Cyclooxygenase-2 (COX-2) is a key enzyme of prostaglandin (PG) synthesis that has been demonstrated to be overexpressed in several types of cancers. The function of COX-2 in tumor progression has been recently elucidated. In tumors in which COX-2 is overexpressed, the antitumor effects are suppressed. We examined the effects of celecoxib, a COX-2 inhibitor, in enhancing the antitumor effects of chemotherapy and radiotherapy for esophageal squamous cell carcinoma (ESCC) by reducing the COX-2 activity. We used the human esophageal squamous cell lines TE2 and T.Tn treated with celecoxib and 5-FU/radiation, after which cell viability assays were performed. Changes in the expressions of dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT) mRNA and PGE2 were also measured. In addition, apoptotic changes, and the invasion and migration activity in both the celecoxib and 5-FU treated cells were evaluated. The experiments showed that T.Tn and TE2 proliferation was strongly inhibited by the combination of 5-FU/radiation and the COX-2 inhibitor. Inhibiting the COX-2 activity induced a reduction in PGE2 levels in TE2/T.Tn cells. Following treatment with the COX-2 inhibitor and 5-FU, the OPRT expression was upregulated and the DPD expression was downregulated in the resistant cells. In addition, the combination treatment with the COX-2 inhibitor and 5-FU markedly inhibited both the cell invasion and migration activity. Therefore, COX-2 inhibitors can be useful enhancers of antitumor drugs and radiotherapy for ESCC.