Aerosolized bexarotene inhibits lung tumorigenesis without increasing plasma triglyceride and cholesterol levels in mice

Qi Zhang, Jing Pan, Jingjie Zhang, Pengyuan Liu, Ruth Chen, Da Ren Chen, Ronald Lubet, Yian Wang, Ming You

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)270-276
Number of pages7
JournalCancer Prevention Research
Volume4
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

Fingerprint

Carcinogenesis
Triglycerides
Cholesterol
Lung
Tumor Burden
Retinoid X Receptors
Neoplasms
Hypertriglyceridemia
Benzo(a)pyrene
Chemoprevention
bexarotene
Hypercholesterolemia
Respiratory System
Inhalation
Rodentia
Lung Neoplasms
Breast
Apoptosis
Diet

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Aerosolized bexarotene inhibits lung tumorigenesis without increasing plasma triglyceride and cholesterol levels in mice. / Zhang, Qi; Pan, Jing; Zhang, Jingjie; Liu, Pengyuan; Chen, Ruth; Chen, Da Ren; Lubet, Ronald; Wang, Yian; You, Ming.

In: Cancer Prevention Research, Vol. 4, No. 2, 02.2011, p. 270-276.

Research output: Contribution to journalArticle

Zhang, Qi ; Pan, Jing ; Zhang, Jingjie ; Liu, Pengyuan ; Chen, Ruth ; Chen, Da Ren ; Lubet, Ronald ; Wang, Yian ; You, Ming. / Aerosolized bexarotene inhibits lung tumorigenesis without increasing plasma triglyceride and cholesterol levels in mice. In: Cancer Prevention Research. 2011 ; Vol. 4, No. 2. pp. 270-276.
@article{7bdf3f4ce77f44bca05343325e484c0d,
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.",
author = "Qi Zhang and Jing Pan and Jingjie Zhang and Pengyuan Liu and Ruth Chen and Chen, {Da Ren} and Ronald Lubet and Yian Wang and Ming You",
year = "2011",
month = "2",
doi = "10.1158/1940-6207.CAPR-10-0246",
language = "English (US)",
volume = "4",
pages = "270--276",
journal = "Cancer Prevention Research",
issn = "1940-6207",
publisher = "American Association for Cancer Research Inc.",
number = "2",

}

TY - JOUR

T1 - Aerosolized bexarotene inhibits lung tumorigenesis without increasing plasma triglyceride and cholesterol levels in mice

AU - Zhang, Qi

AU - Pan, Jing

AU - Zhang, Jingjie

AU - Liu, Pengyuan

AU - Chen, Ruth

AU - Chen, Da Ren

AU - Lubet, Ronald

AU - Wang, Yian

AU - You, Ming

PY - 2011/2

Y1 - 2011/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79551709612&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79551709612&partnerID=8YFLogxK

U2 - 10.1158/1940-6207.CAPR-10-0246

DO - 10.1158/1940-6207.CAPR-10-0246

M3 - Article

C2 - 21163938

AN - SCOPUS:79551709612

VL - 4

SP - 270

EP - 276

JO - Cancer Prevention Research

JF - Cancer Prevention Research

SN - 1940-6207

IS - 2

ER -