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J Thorac Cardiovasc Surg 2003;126:1129-1133
© 2003 The American Association for Thoracic Surgery

General thoracic surgery

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

^a Department of Cardiothoracic Surgery, Hastings Thoracic Oncology Laboratory, Los Angeles, Calif, USA
^b Directors, Hastings Thoracic Oncology Laboratory, Los Angeles, Calif, USA
^c Department of Pathology, Hastings Thoracic Oncology Laboratory, Los Angeles, Calif, USA

Read at the Twenty-seventh Annual Meeting of The Western Thoracic Surgical Association, Big Sky, Mont, June 19-22, 2002.

Received for publication July 9, 2002; revisions received August 19, 2002; revisions received January 16, 2003; accepted for publication March 12, 2003.

^* Address for reprints: Ross M. Bremner, MD, PhD, Department of Cardiothoracic Surgery, Keck School of Medicine, 1510 San Pablo St, Suite 415, Los Angeles, CA 90033, USA
rbremner{at}surgery.usc.edu

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 10⁶ 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 mm³ and for untreated mice were 533.1 ± 453.6 mm³ (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 mm³ and for untreated mice were 809.6 ± 1226.4 mm³ (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.

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