Lentivirus-mediated carboxyl-terminal modulator protein gene transfection via aerosol in lungs of K-ras null mice

Department of Pharmacology, Cancer Research Institute, Research Institute for Medical Sciences, College of Medicine,Chungnam National University, Daejon, KoreaThe low efficiency of conventional therapies in achievinglong-term survival of lung cancer patients calls for develop-ment of novel options. Aerosol gene delivery may provide thealternative for safe and effective treatment for lung cancer.Therefore, current study was performed to elucidate thepotential effects of C-terminal modulator protein (CTMP) viaaerosol on lung tumorigenesis. Lentiviral vector-CTMP wasdelivered into K-ras null lung cancer mice through the nose-only inhalation system for 30 min. After 48 h, the potentialeffects of CTMP on Akt1-related signals and cell cycleregulation in the lungs were evaluated by western blot,immunohistochemistry and zymography. Lentivirus-basedCTMP delivery inhibited the Akt1 activity through selectivesuppression of Akt1 phosphorylation at Ser473. Aerosoldelivery of CTMP inhibited proteins important for Akt1signals, cell cycle and tumor metastasis in lungs of K-rasnull mice. Together, our results suggest that lentivirus-mediated aerosol delivery of CTMP may be compatible withnoninvasive in vivo gene therapy. Our results emphasize theimportance of noninvasive-targeted delivery of CTMP forlung cancer therapy in the future. While the studies areconducted in mice, it is envisioned that noninvasive targetingthe specific genes responsible for cancer progression is anattractive strategy for effective anticancer therapeutics.Gene Therapy (2007) 14, 1721–1730; doi:10.1038/sj.gt.3303042; published online 25 October 2007Keywords: aerosol gene delivery; CTMP; Akt1; lung cancer; lentivirus system