Simultaneous Blockage of Epidermal Growth Factor Receptor and Cyclooxygenase-2 in a Human Xenotransplanted Lung Cancer Model

The effects of erlotinib combined with celecoxib in a lung cancer xenograft model were here explored witha focus on possible mechanisms. A xenotransplanted lung cancer model was established in nude mice using thehuman lung cancer cell A549 cell line and animals demonstrating tumour growth were randomly divided intofour groups: control, erlotinib, celecoxib and combined (erotinib and celecoxib). The tumor major axis andshort diameter were measured twice a week and after 40 days tissues were collected for immunohistochemicalanalyses of Bcl-2 and Bax positive cells and Western-blotting analyses for the epidermal growth factor recepto(EGFR), P-EGFR, and cyclooxygenase-2 (COX-2). Tumor size in the combined group was smaller than in theothers (p<0.01) and the percentage of Bcl-2 positive cells was fewer in most cases (p<0.01), while that of Baxpositive cells was greater than in the erlotinib and celecoxib groups (P>0.05). Western blotting showed decreasedexpression of P-EGFR and COX-2 with both erlotinib and celecoxib treatments, but most pronouncedly in thecombined group (P<0.05). Simultaneous blockage of the EGFR and COX-2 signal pathways exerted strongergrowth effects in our human xenotransplanted lung cancer model than inhibition of either pathway alone. Theanti-tumor effects were accompanied by synergetic inhibition of tumor cell apoptosis, activation of p-EGFR andexpression of COX-2.