Repeated Aerosol Delivery of Carboxyl-terminal Modulator Protein Suppresses Tumor in the Lungs of K-rasLA1 Mice

摘要

Rationale: Difficulties in achieving long-term survival of patients with lung cancer treated with conventional therapies suggest that novel approaches are required. Recent advances in aerosol-mediated gene delivery have provided the possibility of an alternative for the safe and effective treatment of lung cancer.Objectives: To investigate the repeated effect of carboxyl-terminal modulator protein (CTMP) on multistage lung tumorigenesis. In this study, we addressed this question by studying the effects of lentivirus-based CTMP in the lungs of 9- and 13-week-old K-ras^LA1 mice, a model of lung cancer.Methods: An aerosol of lentivirus-based CTMP was delivered into 9- and 13-week-old K-ras^LA1 mice, a model of lung cancer, through a nose-only inhalation system twice a week for 4 weeks. The effects of CTMP on lung cancer progression and Akt-related signals were evaluated.Measurements and Main Results: Long-term repeated delivery of CTMP effectively reduced tumor progression in the lungs at different stages of development. Lentiviral-CTMP inhibited protein synthesis and cell cycle and altered Akt signaling pathway in the lungs of 9-week-old K-ras^LA1 mice, and increased apoptosis was observed in the lungs of 13-week-old K-ras^LA1 mice.Conclusions: Long-term repeated viral delivery of CTMP may provide a useful tool for designing lung tumor treatment.