期刊
JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY
卷 26, 期 3, 页码 165-173出版社
MARY ANN LIEBERT INC
DOI: 10.1089/jamp.2011.0959
关键词
aerosol gene delivery; shRNA AIMP2-DX2; angiogenesis; Akt1 signaling pathway
资金
- National Research Foundation from the Ministry of Education, Science and Technology (MEST) [NRF-2012-0001116, 2012M3A9C4048819]
- Research Institute for Veterinary Science, Seoul National University
- National Research Foundation of Korea [2012M3A9C4048819] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Background: 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. Methods: 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. Results and Conclusions: 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.
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