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Aerosolized bexarotene inhibits lung tumorigenesis without increasing plasma triglyceride and cholesterol levels in
Qi Zhang1, Jing Pan, Jingjie Zhang
1Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA.
Abstract:
Prior studies have shown the retinoid X receptor (RXR) agonist bexarotene has preventive efficacy in rodent models of mammary and lung tumorigenesis albeit causing hypertriglyceridemia and hypercholesterolemia. We reasoned that bexarotene delivered by inhalation may provide sufficient dose directly to the respiratory tract to achieve efficacy while avoiding these side effects. In this study, the chemopreventive activity of aerosolized bexarotene was investigated in the benzo(a)pyrene [B(a)P]-induced mouse lung tumor model as assessed by tumor multiplicity and tumor load. Aerosolized bexarotene significantly decreased tumor multiplicity and tumor load by 43% and 74%, respectively. Our data showed that bexarotene can both inhibit proliferation and promote apoptosis in vivo. Our data also show that aerosolized bexarotene did not increase plasma total cholesterol and triglyceride level compared with diet group. These results indicate that aerosolization may be a safe and effective route of administering bexarotene for chemoprevention of lung cancer.
Insights
Aerosolized bexarotene effectively prevented lung tumors in mice by inhibiting proliferation and promoting apoptosis. This inhalation method avoided side effects like high cholesterol, suggesting a safer approach for lung cancer chemoprevention.
Area of Science:
- Oncology
- Pharmacology
- Respiratory Medicine
Background:
- Retinoid X Receptor (RXR) agonists, like bexarotene, show promise in preventing mammary and lung tumors.
- Systemic administration of bexarotene can cause adverse effects, including hypertriglyceridemia and hypercholesterolemia.
Purpose of the Study:
- To investigate the chemopreventive efficacy of aerosolized bexarotene in a mouse model of lung tumorigenesis.
- To determine if inhalation delivery mitigates the metabolic side effects associated with bexarotene.
Main Methods:
- Utilized the benzo(a)pyrene [B(a)P]-induced mouse lung tumor model.
- Administered bexarotene via aerosolization, targeting direct delivery to the respiratory tract.
- Assessed chemopreventive activity by measuring tumor multiplicity and tumor load.
Main Results:
- Aerosolized bexarotene significantly reduced lung tumor multiplicity by 43% and tumor load by 74%.
- Bexarotene demonstrated in vivo inhibition of tumor cell proliferation and promotion of apoptosis.
- No significant increase in plasma total cholesterol or triglyceride levels was observed compared to the control diet group.
Conclusions:
- Aerosolized bexarotene is a potentially safe and effective strategy for lung cancer chemoprevention.
- Inhalation delivery of bexarotene may circumvent the metabolic side effects observed with systemic administration.
- This approach warrants further investigation for clinical application in lung cancer prevention.
