Abstract
To assess cyclooxygenase-2 inhibition on primary tumor and mediastinal metastases in a murine model of orthotopic lung adenocarcinoma.
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 × 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.
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).
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.