1. ¹Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea
2. ²Laboratory of Biomedical Polymer and Tissue Engineering, School of Agricultural Biotechnology, Seoul National University, Seoul, Korea
3. ³Laboratory of Molecular Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
4. ⁴Laboratory of Cancer Prevention, National Cancer Institute, Frederick, MD, USA
5. ⁵Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA, USA
6. ⁶Graduate Center for Toxicology/Markey Cancer Center, College of Medicine, University of Kentucky, Lexington, KY, USA

Correspondence: Dr M-H Cho, College of Veterinary Medicine, Laboratory of Toxicology, Seoul National University, Sillim-Dong, Seoul 151–742, Korea. E-mail: mchotox@snu.ac.kr

Received 7 September 2006; Revised 4 May 2007; Accepted 14 May 2007; Published online 5 July 2007.

Abstract

The long-term survival of lung cancer patients treated with conventional therapies remains poor and therefore the need for novel approaches remains high. This has led to the re-emergence of aerosol delivery as a therapeutic intervention. In this study, glucosylated polyethylenimine (GPEI) was used as carrier to investigate programmed cell death 4 (PDCD4) and PDCD4 mutant (D418A), an eIF4A-binding mutant, on PDCD4-related signaling and activator protein-1 (AP-1) activity in the lungs of AP-1 luciferase reporter mice. After confirming the efficiency of GPEI as a carrier in lungs, the effects of aerosol-delivered PDCD4 were investigated in AP-1 luciferase reporter mice. Aerosol delivery of GPEI/PDCD4 through a nose-only inhalation facilitated the apoptosis of lungs whereas aerosol PDCD4 mutant did not. Also, such aerosol delivery regulated proteins relevant to cell-cycle control and suppressed AP-1 activity. Results obtained by western blot analysis, immunohistochemistry, luciferase assay and deoxynucleotidyl-transferase-mediated nick end labeling study suggest that combined actions such as facilitating apoptosis, controlling cell cycle and suppression of AP-1 activity by PDCD4 may provide useful tool for designing lung tumor prevention and treatment by which PDCD4 functions as a transformation suppressor in the future.