Abstract
The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Revisiting of aerosol gene delivery may provide an alternative for safe and effective treatment for lung cancer. In this study, imidazole ring-containing urocanic acid-modified chitosan (UAC) designed in the previous study was used as a gene carrier. The potential effects of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) on Akt-related signals and cell cycle regulation were evaluated. Aerosols of UAC–PTEN were delivered into K-rasLA1 lung cancer model mice through the nose-only inhalation system twice a week for total 4 weeks. Delivered PTEN suppressed lung tumor development significantly through nuclear complex formation between PTEN and p53, suppressing Akt-related signals as well as cell cycle regulation. Together, our results suggest that aerosol delivery of UAC–PTEN may be compatible with noninvasive in vivo gene therapy.
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Acknowledgements
This work was partially supported by the grants from the KOSEF (M10534040002-06N3404-00210) of the Ministry of Science and Technology in Korea. MHC, SHC, MW, MSN were supported by the Nano Systems Institute-National Core Research Center (NSI-NCRC) program of KOSEF. HJ, CXX, YSC, JYS, SJP, ESL, SKH, JTK and AMT are also grateful for the award of the BK21 fellowship. KHL was supported by 21C Frontier Functional Human Genome Project (FG03-0601-003-1-0-0) and National Nuclear R&D Program from Ministry of Science and Technology.
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Jin, H., Xu, CX., Kim, HW. et al. Urocanic acid-modified chitosan-mediated PTEN delivery via aerosol suppressed lung tumorigenesis in K-rasLA1 mice. Cancer Gene Ther 15, 275–283 (2008). https://doi.org/10.1038/sj.cgt.7701116
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DOI: https://doi.org/10.1038/sj.cgt.7701116
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