Aerosolized bexarotene inhibits lung tumorigenesis without increasing plasma triglyceride and cholesterol levels in mice. Cancer Prev Res (Phila) 2011 Feb;4(2):270-6
Date
12/18/2010Pubmed ID
21163938DOI
10.1158/1940-6207.CAPR-10-0246Scopus ID
2-s2.0-79551709612 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
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.
Author List
Zhang Q, Pan J, Zhang J, Liu P, Chen R, Chen DR, Lubet R, Wang Y, You MMESH terms used to index this publication - Major topics in bold
Administration, InhalationAnimals
Anticarcinogenic Agents
Apoptosis
Cell Proliferation
Cholesterol
Female
Immunoenzyme Techniques
Lung Neoplasms
Mice
Mice, Inbred A
Tetrahydronaphthalenes
Triglycerides