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Lentivirus-mediated carboxyl-terminal modulator protein gene transfection via aerosol in lungs of K-ras null mice

Gene Therapy volume 14, pages 1721–1730 (2007)Cite this article

Abstract

The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Aerosol gene delivery may provide the alternative for safe and effective treatment for lung cancer. Therefore, current study was performed to elucidate the potential effects of C-terminal modulator protein (CTMP) via aerosol on lung tumorigenesis. Lentiviral vector-CTMP was delivered into K-ras null lung cancer mice through the nose-only inhalation system for 30 min. After 48 h, the potential effects of CTMP on Akt1-related signals and cell cycle regulation in the lungs were evaluated by western blot, immunohistochemistry and zymography. Lentivirus-based CTMP delivery inhibited the Akt1 activity through selective suppression of Akt1 phosphorylation at Ser473. Aerosol delivery of CTMP inhibited proteins important for Akt1 signals, cell cycle and tumor metastasis in lungs of K-ras null mice. Together, our results suggest that lentivirus-mediated aerosol delivery of CTMP may be compatible with noninvasive in vivo gene therapy. Our results emphasize the importance of noninvasive-targeted delivery of CTMP for lung cancer therapy in the future. While the studies are conducted in mice, it is envisioned that noninvasive targeting the specific genes responsible for cancer progression is an attractive strategy for effective anticancer therapeutics.

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Acknowledgements

This work was partially supported by the grants from the Korea Research Foundation (KRF-2006-311-E00507) in Korea. MHC and SHC were supported by the Nano Systems Institute-National Core Research Center (NSI-NCRC) program of KOSEF. SKH, JTK, SJP, ESL, YSC 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. GRB Jr was supported by National Cancer Institute Grant CA84573.

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Authors and Affiliations

  1. Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea

    S-K Hwang, J-T Kwon, S-J Park, S-H Chang, E-S Lee, Y-S Chung & M-H Cho

  2. Nano Systems Institute-National Core Research Center, Seoul National University, Seoul, Korea

    S-H Chang & M-H Cho

  3. Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA, USA

    G R Beck Jr

  4. Laboratory of Molecular Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, Korea

    K H Lee

  5. Department of Pharmacology, Cancer Research Institute, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejon, Korea

    L Piao & J Park

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  1. S-K Hwang
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Correspondence to M-H Cho.

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Hwang, SK., Kwon, JT., Park, SJ. et al. Lentivirus-mediated carboxyl-terminal modulator protein gene transfection via aerosol in lungs of K-ras null mice. Gene Ther 14, 1721–1730 (2007). https://doi.org/10.1038/sj.gt.3303042

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