Our previous study comparing inhalation and aspiration to administer agents directly to lung indicated that aspiration route is as effective as inhalation while reducing costs for equipment and chemopreventive agent. This study evaluated the chemopreventive efficacy and mechanism of
licofelone, a dual inhibitor of COX-2 and
5-lipoxygenase (5-Lox), via oropharyngeal aspiration against mouse lung
adenoma. Eight-week-old female A/J mice were given three doses of
benzo[a]pyrene (B[a]
P; 2 mg/dose, gavage) to induce lung
adenomas. After dysplasia developed, the mice were given
licofelone (0, 0.03, 0.1, or 0.3 mg/kg) for 16 weeks, and
tumor incidence and multiplicity in lung were measured. In addition, the expression of a series of
biomarkers in
lung cancer progression was evaluated at 2 and 16 weeks.
Licofelone showed dose-related inhibition of B[a]P-induced
tumor incidence and multiplicity at 0.03 and 0.1 mg/kg following 16-week treatment.
Licofelone also showed dose-dependent inhibition of COX-2 (25%-41%) and 5-Lox (35%-61%) at 2 and 16 weeks and
proliferating cell nuclear antigen (
PCNA; 41%-61%) at 16 weeks. A dose-dependent increase in apoptosis (1.5- to 2.4-fold) was also observed in
licofelone groups. A marginal inhibition of
survivin was observed at one dose. In conclusion, this study showed that
licofelone via aspiration showed chemopreventive efficacy against mouse lung
adenoma with good correlation to early and late
biomarkers of
lung cancer progression. This is the first study to show that the aspiration route can be an excellent inexpensive alternative to inhalation for direct delivery of drugs to rodent lungs for efficacy testing of potential chemopreventive agents.