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


OBJECTIVE
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.


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.
Hwang
Soon-Kyung
SK
Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
Lim
Hwang-Tae
HT
Minai-Tehrani
Arash
A
Lee
Eun-Sun
ES
Park
Jongmin
J
Park
Seung Bum
SB
Beck
George R
GR
Cho
Myung-Haing
MH
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000336:Aerosols; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002352:Carrier Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D011905:Genes, ras; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010170:Palmitoyl-CoA Hydrolase; D016896:Treatment Outcome
D000336:Aerosols; D002352:Carrier Proteins; C527670:CTMP protein, mouse; D010170:Palmitoyl-CoA Hydrolase