Cyclooxygenase-2 inhibition decreases primary and metastatic tumor burden in a murine model of orthotopic lung adenocarcinoma.

OBJECTIVE: To assess cyclooxygenase-2 inhibition on primary tumor and mediastinal metastases in a murine model of orthotopic lung adenocarcinoma. METHODS: Human lung adenocarcinoma cells (CRL5908, female nonsmoker with cyclooxygenase-2 expression by Western blot) were implanted under direct visualization through the parietal pleura in the upper lobe of the left lung (2 x 10(6) cells/animal) of SCID mice. Mice were randomly assigned to 2 groups, either untreated (n = 62) or celecoxib-treated (n = 60). Celecoxib, a selective cyclooxygenase-2 antagonist, was solubilized in the animals' drink (25 mg/kg per day). Mice were arbitrarily killed at 1, 2, 3, and 4 weeks. A blinded observer assessed primary tumor volume and metastatic disease grossly and histologically. RESULTS: Gross metastatic lymph nodes were present at 3 weeks in none of 15 (0%) treated and 12 of 15 (80.0%) untreated animals (P <.0001). Mean primary tumor volumes at 3 weeks for treated mice were 7.9 +/- 10.0 mm(3) and for untreated mice were 533.1 +/- 453.6 mm(3) (mean +/- SD, P <.0001). Gross metastatic lymph nodes were present at 4 weeks in 3 of 15 (20%) treated and 17 of 17 (100%) untreated animals (P <.0001). Mean primary tumor volumes at 4 weeks for treated mice were 37.1 +/- 46.2 mm(3) and for untreated mice were 809.6 +/- 1226.4 mm(3) (mean +/- SD, P <.0001). Mean blood levels of celecoxib in treated mice were 236.8 +/- 34.2 ng/mL (mean +/- SD). CONCLUSIONS: Cyclooxygenase-2 inhibition results in decreased primary and metastatic tumor burden in a murine model using human lung adenocarcinoma. Cyclooxygenase-2 inhibition has the potential to decrease tumor progression and metastases in patients with lung adenocarcinoma.