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Aerosol delivery of eukaryotic translation initiation factor 4E-binding protein 1 effectively suppresses lung tumorigenesis in K-rasLA1 mice

Cancer Gene Therapy volume 20, pages 331–335 (2013)Cite this article

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Abstract

Conventional radiotherapy or chemotherapy for the long-term survival of patients with lung cancer is still difficult for treatment in metastatic and advanced tumors. Therefore, the safe and effective approaches to the treatment of lung cancer are needed. In this study, the effect of delivered eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) on lung cancer progression was evaluated. Recombinant adeno-associated virus (rAAV)-M3/4E-BP1 was delivered into 6-week-old K-rasLA1 lung cancer model mice through a nose-only inhalation system twice a week for 4 weeks. Long-term repeated delivery of 4E-BP1 effectively reduced tumor progression in the lungs of K-rasLA1 mice. Reduction of eIF4E by overexpression of 4E-BP1 resulted in suppression of cap-dependent protein expression of basic fibroblast growth factor (bFGF or FGF-2) and vascular endothelial growth factor (VEGF). In addition, delivered 4E-BP1 inhibited the proliferation of lung cancer cells in K-rasLA1 mice model. Our results suggest that long-term repeated viral delivery of 4E-BP1 may provide a useful tool for designing lung cancer treatment.

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Acknowledgements

Part of this work was supported by the National Research Foundation grant (2012M3A9B6055304) funded by the Korea government (MEST). M-HC was also partially supported by the Research Institute for Veterinary Science, Seoul National University, Seoul, Korea.

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Author notes

  1. S-H Chang and J-E Kim: The first two authors contributed equally to this work.

Authors and Affiliations

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

    S-H Chang, J-E Kim, J-H Lee, A Minai-Tehrani & M-H Cho

  2. Department of Nanofusion Technology, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea

    J-E Kim & M-H Cho

  3. Laboratory of Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Korea

    K Han & C Chae

  4. Juseong Gene Therapy R&D Center, Juseong University, Chung-buk, Korea

    Y-H Cho, J-H Yun & K Park

  5. Department of Smart Foods and Drugs and Indang Institute of Molecular Biology, Inje University, Seoul, Korea

    Y-S Kim

  6. Graduate Group of Tumor Biology, Seoul National University, Seoul, Korea

    M-H Cho

  7. Advanced Institute of Convergence Technology, Seoul National University, Suwon, Korea

    M-H Cho

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  1. S-H Chang
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Correspondence to M-H Cho.

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Chang, SH., Kim, JE., Lee, JH. et al. Aerosol delivery of eukaryotic translation initiation factor 4E-binding protein 1 effectively suppresses lung tumorigenesis in K-rasLA1 mice. Cancer Gene Ther 20, 331–335 (2013). https://doi.org/10.1038/cgt.2013.24

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