Study on growth suppression and chemoprevention of lung cancer by cyclooxygenase 2 inhibitor

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We recently reported that an increased expression of COX-2 was frequently seen in a specific type of lung cancer, i.e., adenocarcinoma, and was possibly associated with its invasion and metastases. We have also shown the presence of a significant relationship between elevated COX-2 expression and shortened patient survival in a cohort of patients with stage I disease.We report here that COX-2 inhibitor could inhibit proliferation of non-small cell lung cancer (NSCLC) cell lines in vitro in a dose-dependent manner, in part by inducing apoptosis even at clinically achievable low concentrations. Our observations also suggested that the state of COX-2 expression in NSCLC cells might influence their responsiveness to COX-2 inhibitors. Moreover, we found that COX-2 inhibitor, when used in combination at clinically achievable concentrations, reduced the IC_<50> values of various anticancer agents by up to 77%, although the levels of reduction varied considerably. In radiation sensitivity, COX-2 inhibitor was shown to have an additive effect on the efficacy of irradiation. Since our previous studies have indicated that significantly increased COX-2 expression is present in up to 70% of adenocarcinoma cases, the present findings are of great clinical interest and the recent development of next generation, highly selective COX-2 inhibitors should lead to even greater efficacy for the adjunct use with various anticancer agents in the treatment of high risk patients without compromising their quality of life.