Aerosol-Based Gene Therapy Effective in Lung Cancer Model

Akt is involved in cellular survival pathways through inhibition of apoptotic processes. It induces protein synthesis pathways, and is, therefore, a key signaling protein in the cellular pathways that lead to skeletal muscle hypertrophy and general tissue growth. Since it can block apoptosis, and thereby promote cell survival, Akt has been implicated as a major factor in many types of cancer.

To block cancer cell Akt activity the investigators sought to implant the gene for carboxyl-terminal modulator protein (CTMP), a negative regulator of Akt signaling. The study was carried out using the K-ras mouse experimental lung cancer model. To transfer the gene the investigators used an aerosol of lentivirus-based CTMP, which was delivered into nine- and 13-week-old K-ras mice through a nose-only inhalation system twice a week for four weeks. The effects of CTMP on lung cancer progression and Akt-related signals were evaluated.

Results published in the June 15, 2009, issue of the American Journal of Respiratory and Critical Care Medicine revealed that the 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 the Akt signaling pathway in the lungs of the nine-week-old K-ras mice, and increased apoptosis was observed in the lungs of the13-week-old mice. No such effects were seen in control mice that received the vector alone or those left untreated.

"Aerosol delivery targets the lungs specifically and represents a noninvasive alternative for targeting genes to the lung,” said senior author Dr. Myung-Haing Cho, professor of chemistry at Seoul National University. "The delivery of genes via aerosol holds promise for the treatment of a broad spectrum of pulmonary disorders and offers numerous advantages over more invasive modes of delivery.”

"Our results demonstrated that lentivirus-mediated CTMP overexpression suppressed Akt activity and inhibited tumor progression,” said Dr. Cho. "Repeated aerosol gene delivery may provide an effective noninvasive model of gene delivery and understanding the role of CTMP in the multistage lung tumorigenesis may be essential in developing effective therapeutics for lung cancer.”


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Seoul National University