PT  - JOURNAL ARTICLE
AU  - Jin Woo Kim
AU  - Chang Dong Yeo
AU  - Jong Min Lee
AU  - Hyeon Hui Kang
AU  - Sang Haak Lee
TI  - Chemopreventive effect of phosphodieasterase-4 inhibition in benzo(a)pyrene-induced murine lung cancer model
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - P2697
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/P2697.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/P2697.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - Cigarette smoking increase chronic airway inflammation and oxidative stress, which may result in chronic obstructive respiratory disease (COPD) and tumor growth. We assessed the impact of rolipram, a selective PDE4 inhibitor, on chemoprevention in benzo(a)pyrene-induced lung cancer model in mice. Female A/J mice were given a single dose of benzo(a)pyrene as the carcinogen. Intraperitoneal administration of rolipram began 2 weeks post-carcinogen treatment and continued triweekly for 28 weeks. Tumor load was determined by averaging the total tumor volume in each group. Tumor tissues were blocked and incubated with primary antibody against proliferating cell nuclear antigen (Ki67). Benzo(a)pyrene induced an average of 10.4 ± 1.7 tumors per mouse (Figure 1). Average tumor load in benzo(a)pyrene was 25.9 ± 3.8 mm3 (Figure 1). Rolipram treatment significantly decreased tumor multiplicity by 45.1% and tumor load 52.9% when compared to the benzo(a)pyrene group. The number of proliferating cells on tumors stained with Ki67 was significantly reduced in rolipram-treated mice compared with benzo(a)pyrene-treated mice. In vitro experiments using benzo(a)pyrene-induced lung cancer model showed that PDE4 inhibition exhibited inhibitory effects on lung carcinogenesis. Our results provide evidence that PDE4 inhibitor could be a promising chemopreventive agent in high risk groups for lung cancer, for example, smokers and patients with COPD.