title: Aerosolized bexarotene inhibits lung tumorigenesis without increasing plasma triglyceride and cholesterol levels in mice.
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.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.forename: Jingjie
authors.initials: J
authors.lastname: Zhang
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Liu
authors.forename: Ruth
authors.initials: R
authors.lastname: Chen
authors.forename: Da-ren
authors.initials: DR
authors.lastname: Chen
authors.forename: Ronald
authors.initials: R
authors.lastname: Lubet
authors.forename: Yian
authors.initials: Y
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: You
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D000077610:Bexarotene; D049109:Cell Proliferation / Q000187:drug effects; D002784:Cholesterol / Q000097:blood*; D005260:Female; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000097:blood / Q000473:pathology* / Q000517:prevention & control*; D051379:Mice; D008805:Mice, Inbred A; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood*
chemical_list: D016588:Anticarcinogenic Agents; D013764:Tetrahydronaphthalenes; D014280:Triglycerides; D002784:Cholesterol; D000077610:Bexarotene