BLOCKADE OF EPIDERMAL GROWTH FACTOR RECEPTOR, CYCLOXYGENASE-2 (COX-2) AND MAMMALIAN TARGET OF RAPAMYCIN (M-TOR) IN ANIMAL MODEL OF LUNG CANCER

Abstract

To explore the effectiveness and possible toxicity of the use of epidermal growth factor receptor inhibitor (EGFR Inhibitor), Celecoxib (COX2 inhibitor) and Sirolimus (m-TOR inhibitor) as single agents and drug combinations for the treatment of lung cancer in an experimental model. Lung cancer was induced in Balb-C mice by intraperitoneal injection urethane. Mice were treated with water (control) , Erlotinib (E) (50 mg/kg), Celecoxib (X) (50 mg/kg), Sirolimus (R) (2 mg/kg) given alone and in the following doublet and triplet combinations in the same dosages for 7 days. The number of pulmonary nodules in the combined treatment was significantly inhibited compared with control (p=0.010); E (p=0.028), EX (p=0.010), ERX (p=0.040) showed a smaller number of statistically significant nodules. Regarding coat changes we observe statistically significant differences among groups (p<0.001) where ERX and ER had a higher occurrence of this change. There was a higher incidence of skin rashes in groups: E (p<0.001), ER (p<0.0001), and ERX (p<0.001). Regarding weight we identify weight loss in the ERX (p=0.025). The combination of EGFR inhibitor, COX-2 inhibitor and m-TOR inhibitor had anti-tumor activity in experimental lung cancer. The combination of Celecoxib treatment with Erlotinib is a suggestion for decrease of dermatological events in patients. The combination of EGFR inhibitor and Sirolimus does not decrease the number of lung nodules and potentiates adverse events.