Lentivirus-mediated carboxyl-terminal modulator protein gene transfection via aerosol in lungs of K-ras null mice
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Updated: Jul 10, 2026
Protein Transfection of Mouse Lung
Published on: May 15, 2013
S-K Hwang1, J-T Kwon, S-J Park
1Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
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.
Insights
Novel aerosol gene therapy using C-terminal modulator protein (CTMP) effectively inhibited lung cancer progression in mice. This noninvasive approach targets key cancer-related signals, offering a promising new avenue for lung cancer treatment.
Area of Science:
- Oncology
- Gene Therapy
- Respiratory Medicine
Background:
- Conventional lung cancer therapies have limited long-term survival rates.
- Aerosol gene delivery presents a potential noninvasive treatment strategy.
- The C-terminal modulator protein (CTMP) role in lung tumorigenesis requires further investigation.
Purpose of the Study:
- To investigate the effects of aerosol-delivered C-terminal modulator protein (CTMP) on lung cancer development.
- To evaluate CTMP's impact on Akt1 signaling pathways and cell cycle regulation in lung tumors.
- To assess the feasibility of lentivirus-mediated aerosol gene delivery for lung cancer therapy.
Main Methods:
- Lentiviral vector carrying CTMP was administered to K-ras null lung cancer mice via a nose-only inhalation system.
- Effects on Akt1-related signals and cell cycle regulation were analyzed using western blot, immunohistochemistry, and zymography.
- Tumorigenesis and metastasis-associated proteins were quantified 48 hours post-delivery.
Main Results:
- Aerosol delivery of lentivirus-CTMP selectively inhibited Akt1 phosphorylation at Ser473, reducing Akt1 activity.
- CTMP delivery suppressed key proteins involved in Akt1 signaling, cell cycle progression, and tumor metastasis.
- The treatment demonstrated efficacy in reducing lung tumor progression in the K-ras null mouse model.
Conclusions:
- Lentivirus-mediated aerosol delivery of CTMP is a viable noninvasive gene therapy approach for lung cancer.
- Targeted delivery of CTMP shows potential for inhibiting lung tumorigenesis and metastasis.
- This strategy holds promise for future noninvasive, targeted gene therapies against lung cancer.
