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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

12/18/2010

Pubmed ID

21163938

DOI

10.1158/1940-6207.CAPR-10-0246

Scopus ID

2-s2.0-79551709612   18 Citations

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.

Author List

Zhang Q, Pan J, Zhang J, Liu P, Chen R, Chen DR, Lubet R, Wang Y, You M

Authors

Pengyuan Liu PhD Adjunct Professor in the Physiology department at Medical College of Wisconsin
Jing Pan PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Yian Wang MD, PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Ming You MD, PhD Associate Provost, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Qi Zhang PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Administration, Inhalation
Animals
Anticarcinogenic Agents
Apoptosis
Cell Proliferation
Cholesterol
Female
Immunoenzyme Techniques
Lung Neoplasms
Mice
Mice, Inbred A
Tetrahydronaphthalenes
Triglycerides
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d