P1.01-011 Roflumilast Attenuates Benzo(a)Pyrene-Induced Lung Cancer via Suppression of Airway Inflammation in Murine Model

Abstract

Chronic airway inflammation has been emerging targets for lung cancer chemoprevention as well as treatment of COPD. The aim of the present study was to determine the role of roflumilast and aerosolized budesonide in benzo(a)pyrene-induced lung cancer in mice and to elucidate the possible their mechanisms. Female A/J mice were given a single dose of benzo(a)pyrene. Intraperitoneal administration of roflumilast (1mg/kg, 5mg/kg) began 2 weeks post-carcinogen treatment and continued tri-weekly for 28 weeks. Aerosolized budesonide was administered by aerosol delivery for 2 min/day and 5 days/week. Tumor load was determined by averaging the total tumor volume in each group. Benzo(a)pyrene induced an average tumor size of 9.4 ± 1.8 tumors per mouse, with an average tumor load of 19.5 ± 3.8mm3. Roflumilast treatment at 1 and 5 mg/kg did not inhibit tumor number, however, reduced tumor load, an average of 8.8 ± 2.0 mm3 at 5mg/kg treatment, significantly. Aerosolized budesonide administration did not show reductions of tumor number or load. The decreased expressions of cyclic AMP and protein kinase A caused by benzo(a)pyrene were increased by roflumilast treatment. NF-κB expression in tumor tissues was lower in the roflumilast group than the place group. In vivo experiments in the benzo(a)pyrene-induced model of lung cancer show that roflumilast significant inhibits tumorigenicity via suppression of inflammation. Possible mechanisms between cAMP pathway and lung cancer development will needed to be determined.