Lentivirus-AIMP2-DX2 shRNA Suppresses Cell Proliferation by Regulating Akt1 Signaling Pathway in the Lungs of AIMP2+/― Mice

The long-term survival of lung cancer patients treated with conventional therapies remains poor and has changed little in decades. The need for novel approaches remains urgent. Aerosol-mediated delivery of genes has potential for the treatment of a broad spectrum of pulmonary disorders and may offer...

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Veröffentlicht in:Journal of aerosol medicine 2013-06, Vol.26 (3), p.165-173
Hauptverfasser: HWANG, Soon-Kyung, CHANG, Seung-Hee, MINAI-TEHRANI, Arash, KIM, Yeon-Soo, CHO, Myung-Haing
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container_end_page 173
container_issue 3
container_start_page 165
container_title Journal of aerosol medicine
container_volume 26
creator HWANG, Soon-Kyung
CHANG, Seung-Hee
MINAI-TEHRANI, Arash
KIM, Yeon-Soo
CHO, Myung-Haing
description The long-term survival of lung cancer patients treated with conventional therapies remains poor and has changed little in decades. The need for novel approaches remains urgent. Aerosol-mediated delivery of genes has potential for the treatment of a broad spectrum of pulmonary disorders and may offer numerous advantages over invasive modes of delivery. The potential effects of aerosol-delivered lentiviral-based short hairpin AIMP2 lacking exon 2 (shDX2) on lung tumorigenesis were studied. Lentiviral-based shDX2 was delivered into AIMP2(+/-) mice through a nose-only inhalation system twice a week for 4 weeks. The effects of shDX2 on lung cancer progression and the Akt1-mTOR-p70S6K signaling pathway were evaluated. Long-term repeated delivery of lentiviral-based shDX2 suppressed lung tumor progression significantly by inhibiting Akt1-related signals and decreasing both protein synthesis and angiogenesis. In vivo, the aerosol-mediated application of lentiviral-based short hairpin RNAs was successful in achieving potent and specific knockdown of the target. The collective results indicate the therapeutic potential of the repeated delivery of shDX2 for lung cancer treatment and prevention.
doi_str_mv 10.1089/jamp.2011.0959
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subjects Administration, Inhalation
Aerosols
Amino Acyl-tRNA Synthetases - genetics
Animals
Biological and medical sciences
Cell Proliferation
Disease Progression
Gene Knockdown Techniques
Gene Transfer Techniques
General pharmacology
Lentivirus - genetics
Lung - metabolism
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Male
Medical sciences
Mice
Neovascularization, Pathologic - prevention & control
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Proto-Oncogene Proteins c-akt - metabolism
RNA, Small Interfering - administration & dosage
Signal Transduction
title Lentivirus-AIMP2-DX2 shRNA Suppresses Cell Proliferation by Regulating Akt1 Signaling Pathway in the Lungs of AIMP2+/― Mice
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