Cyclooxygenase-2 and epidermal growth factor receptor inhibition in an orthotopic murine model of human lung adenocarcinoma

Abstract

7362 Background: Activated epidermal growth factor receptors (EGFR) and cyclooxygenase-2 (COX-2) enzyme play a related role in growth, apoptosis, angiogenesis, and metastatic spread of lung cancer. Inhibition of these targets using orally available agents is a potential therapeutic strategy for non-small cell lung cancer (NSCLC). We aim to establish the effect of EGFR and COX-2 blockade on growth and metastatic spread in an orthotopic murine model of lung adenocarcinoma. Methods: Human lung adenocarcinoma cells expressing EGFR and COX-2 (ATCC-CRL5908) were implanted in the left upper lobe of SCID mice (2×106 cells/25uL). Mice were randomly assigned to one of 3 treatments at the time of implantation (n=10/group); normal chow, celecoxib (25mg/kg body weight/day), erlotinib (OSI-774) (15mg/kg body weight/day). At 3 weeks mice were killed and a blinded observer measured primary tumor volume and mediastinal metastatic disease. Primary and mediastinal tumor was confirmed histologically and EGFR and COX-2 expres...