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Intranasal Iloprost Prevents Tumors in a Murine Lung Carcinogenesis Model
Meredith A Tennis1, Alex J Smith1, Lori D Dwyer-Nield2
1Division of Pulmonary Sciences and Critical Care Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Abstract:
Lung cancer chemoprevention with the prostacyclin analogue iloprost is the most promising approach to date for intercepting progression of premalignant lung lesions in former smokers. Previous preclinical studies of iloprost used oral delivery, but a study modeling delivery directly to the target organ was needed. In vivo and in vitro studies have identified gene expression changes following iloprost treatment, including increased e-cadherin and Ppargγ and decreased COX2 and vimentin. We used tumor counts and gene expression to demonstrate the effectiveness of intranasal delivery of iloprost in a murine model of premalignant adenomas. Intranasal delivery of iloprost reduced adenoma multiplicity 14 weeks after urethane exposure in FVB/N mice compared with untreated urethane controls. Intranasal iloprost reversed urethane-induced gene expression changes in tumors and whole lung. These results correspond to previous studies of oral iloprost and in vitro treatment of human bronchial epithelial cells. This study demonstrates that intranasal delivery of iloprost in a mouse model of lung premalignant lesions is effective chemoprevention. This will be an essential tool for exploring mechanisms and outcomes of iloprost chemoprevention, along with supporting ongoing clinical trials of inhaled iloprost chemoprevention. PREVENTION RELEVANCE: Iloprost is a promising chemoprevention agent for lung cancer and this work describes a new delivery approach in vivo.
Insights
Intranasal iloprost effectively prevents lung cancer progression in mice with premalignant lesions. This novel delivery method supports ongoing clinical trials for inhaled iloprost chemoprevention in former smokers.
Area of Science:
- Oncology
- Pharmacology
- Pulmonology
Background:
- Lung cancer chemoprevention is crucial for intercepting premalignant lesions, especially in former smokers.
- Iloprost, a prostacyclin analogue, shows promise, but optimal delivery methods require further investigation.
- Previous studies utilized oral delivery, necessitating research into direct organ delivery for enhanced efficacy.
Purpose of the Study:
- To evaluate the effectiveness of intranasal iloprost delivery for lung cancer chemoprevention.
- To assess the impact of intranasal iloprost on premalignant lung adenomas in a murine model.
- To analyze gene expression changes associated with intranasal iloprost treatment in lung tissues.
Main Methods:
- Utilized a murine model of urethane-induced premalignant lung adenomas (FVB/N mice).
- Administered iloprost via intranasal delivery and assessed adenoma multiplicity at 14 weeks.
- Analyzed gene expression changes (e.g., e-cadherin, Ppargγ, COX2, vimentin) in tumors and whole lung tissue.
Main Results:
- Intranasal iloprost significantly reduced adenoma multiplicity compared to controls.
- Iloprost treatment reversed urethane-induced gene expression alterations in lung tumors and tissues.
- Findings align with previous studies on oral iloprost and in vitro human bronchial epithelial cell treatments.
Conclusions:
- Intranasal iloprost demonstrates efficacy as a chemoprevention strategy for lung premalignant lesions in vivo.
- This delivery approach provides a valuable tool for mechanistic studies of iloprost chemoprevention.
- The findings support ongoing clinical trials investigating inhaled iloprost for lung cancer prevention.
