Repeated aerosol delivery of carboxyl-terminal modulator protein suppresses tumor in the lungs of K-rasLA1 mice.

Abstract

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.

• Authors: Soon-Kyung Hwang, Hwang-Tae Lim, Arash Minai-Tehrani, Eun-Sun Lee, Jongmin Park, Seung Bum Park, George R Beck Jr, Myung-Haing Cho
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 179 Issue 12 Pg. 1131-40 (Jun 15 2009) ISSN: 1535-4970 [Electronic] United States
• PMID: 19286625 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aerosols
• Carrier Proteins
• CTMP protein, mouse
• Palmitoyl-CoA Hydrolase

Topics

• Adenocarcinoma (genetics, pathology, therapy)
• Aerosols
• Animals
• Apoptosis
• Blotting, Western
• Carrier Proteins (administration & dosage, biosynthesis, genetics)
• Cell Line, Tumor
• Disease Progression
• Gene Expression Regulation, Neoplastic
• Gene Transfer Techniques
• Genes, ras
• In Situ Nick-End Labeling
• Lung Neoplasms (genetics, pathology, therapy)
• Male
• Mice
• Mice, Inbred C57BL
• Neoplasms, Experimental (drug therapy, genetics, pathology)
• Palmitoyl-CoA Hydrolase
• Treatment Outcome