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Repeated Aerosol Delivery of Carboxyl-terminal Modulator Protein Suppresses Tumor in the Lungs of K-ras^LA1 Mice

¹ Laboratory of Toxicology, College of Veterinary Medicine, ² Nano Systems Institute–National Core Research Center, and ³ Department of Chemistry, College of Natural Science, Seoul National University, Seoul, Korea; and ⁴ Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, Georgia

Correspondence and requests for reprints should be addressed to Myung-Haing Cho, D.V.M., Ph.D., Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea. E-mail: mchotox{at}snu.ac.kr

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.

Key Words: lentivirus • carboxyl-terminal modulator protein • lung cancer • K-ras^LA1 mice • aerosol gene delivery

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Difficulties in achieving long-term survival of lung cancer patients require novel approaches for safe and effective treatment. What This Study Adds to the Field Long-term repeated viral delivery of carboxyl-terminal modulator protein may provide a useful tool for designing lung tumor treatment.